PT1899329E - Derivados de benzimidazole substituídos por pirimidina como inibidores de proteína quinase - Google Patents

Info

Publication number

PT1899329E

PT1899329E PT06774386T PT06774386T PT1899329E PT 1899329 E PT1899329 E PT 1899329E PT 06774386 T PT06774386 T PT 06774386T PT 06774386 T PT06774386 T PT 06774386T PT 1899329 E PT1899329 E PT 1899329E

Authority

PT

Portugal

Prior art keywords

methyl

pyrimidin

benzoimidazol

phenyl

ylamino

Prior art date

2005-07-01

Links

• Espacenet
• Global Dossier
• Discuss

• -1 Pyrimidine-substituted benzimidazole Chemical class 0.000 title claims description 309
• 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 title description 2
• 239000003909 protein kinase inhibitor Substances 0.000 title description 2
• 229940058303 antinematodal benzimidazole derivative Drugs 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 144
• 102100027842 Fibroblast growth factor receptor 3 Human genes 0.000 claims abstract description 22
• 101710182396 Fibroblast growth factor receptor 3 Proteins 0.000 claims abstract description 22
• 108060006706 SRC Proteins 0.000 claims abstract description 13
• 102000001332 SRC Human genes 0.000 claims abstract description 13
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
• 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 claims abstract description 9
• 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 claims abstract description 8
• 229910052736 halogen Inorganic materials 0.000 claims description 69
• 150000002367 halogens Chemical class 0.000 claims description 68
• 125000000217 alkyl group Chemical group 0.000 claims description 59
• 108091000080 Phosphotransferase Proteins 0.000 claims description 40
• 102000020233 phosphotransferase Human genes 0.000 claims description 40
• 239000001257 hydrogen Substances 0.000 claims description 39
• 229910052739 hydrogen Inorganic materials 0.000 claims description 39
• 201000010099 disease Diseases 0.000 claims description 36
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 36
• 125000001072 heteroaryl group Chemical group 0.000 claims description 31
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 30
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 29
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 28
• 238000011282 treatment Methods 0.000 claims description 25
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 24
• 150000003254 radicals Chemical class 0.000 claims description 24
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 22
• 150000003839 salts Chemical class 0.000 claims description 22
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 18
• 125000003545 alkoxy group Chemical group 0.000 claims description 17
• 125000003118 aryl group Chemical group 0.000 claims description 17
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 16
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 15
• 101150028321 Lck gene Proteins 0.000 claims description 12
• 101100481408 Danio rerio tie2 gene Proteins 0.000 claims description 11
• 101100481410 Mus musculus Tek gene Proteins 0.000 claims description 11
• 101150056950 Ntrk2 gene Proteins 0.000 claims description 11
• 108010029869 Proto-Oncogene Proteins c-raf Proteins 0.000 claims description 11
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
• 102100031167 Tyrosine-protein kinase CSK Human genes 0.000 claims description 10
• 125000002947 alkylene group Chemical group 0.000 claims description 10
• 239000003814 drug Substances 0.000 claims description 10
• 101150003567 Mapk12 gene Proteins 0.000 claims description 9
• 108700015929 Mitogen-activated protein kinase 12 Proteins 0.000 claims description 9
• 102000056243 Mitogen-activated protein kinase 12 Human genes 0.000 claims description 9
• 101150105578 SAPK3 gene Proteins 0.000 claims description 9
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
• 102100027907 Cytoplasmic tyrosine-protein kinase BMX Human genes 0.000 claims description 8
• 101000742982 Homo sapiens Serine/threonine-protein kinase WNK3 Proteins 0.000 claims description 8
• 101000997832 Homo sapiens Tyrosine-protein kinase JAK2 Proteins 0.000 claims description 8
• 101000934996 Homo sapiens Tyrosine-protein kinase JAK3 Proteins 0.000 claims description 8
• 102100038115 Serine/threonine-protein kinase WNK3 Human genes 0.000 claims description 8
• 102100033444 Tyrosine-protein kinase JAK2 Human genes 0.000 claims description 8
• 102100025387 Tyrosine-protein kinase JAK3 Human genes 0.000 claims description 8
• 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims description 8
• 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims description 8
• 230000001404 mediated effect Effects 0.000 claims description 8
• YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims description 8
• 101100354317 Mus musculus Ptk6 gene Proteins 0.000 claims description 7
• 101150083487 SIK1 gene Proteins 0.000 claims description 7
• 102100032771 Serine/threonine-protein kinase SIK1 Human genes 0.000 claims description 7
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 7
• 229910052757 nitrogen Inorganic materials 0.000 claims description 7
• 125000001424 substituent group Chemical group 0.000 claims description 7
• 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 6
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
• 125000004076 pyridyl group Chemical group 0.000 claims description 6
• 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 5
• 125000004193 piperazinyl group Chemical group 0.000 claims description 5
• 229920006395 saturated elastomer Polymers 0.000 claims description 5
• MABPYIPHMYIDIF-UHFFFAOYSA-N 3-[[1-(6-aminopyrimidin-4-yl)benzimidazol-2-yl]amino]-4-methyl-n-[4-(2-methylimidazol-1-yl)-3-(trifluoromethyl)phenyl]benzamide Chemical compound CC1=NC=CN1C(C(=C1)C(F)(F)F)=CC=C1NC(=O)C1=CC=C(C)C(NC=2N(C3=CC=CC=C3N=2)C=2N=CN=C(N)C=2)=C1 MABPYIPHMYIDIF-UHFFFAOYSA-N 0.000 claims description 4
• 101100240519 Caenorhabditis elegans nhr-13 gene Proteins 0.000 claims description 4
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
• 125000002950 monocyclic group Chemical group 0.000 claims description 4
• 125000003386 piperidinyl group Chemical group 0.000 claims description 4
• 238000002360 preparation method Methods 0.000 claims description 4
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
• MQDQPOHOVUJCRE-UHFFFAOYSA-N 1-(6-aminopyrimidin-4-yl)-n-(2-methyl-5-nitrophenyl)benzimidazol-2-amine Chemical compound CC1=CC=C([N+]([O-])=O)C=C1NC1=NC2=CC=CC=C2N1C1=CC(N)=NC=N1 MQDQPOHOVUJCRE-UHFFFAOYSA-N 0.000 claims description 3
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 3
• 125000002619 bicyclic group Chemical group 0.000 claims description 3
• 125000004432 carbon atom Chemical group C* 0.000 claims description 3
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
• 125000002541 furyl group Chemical group 0.000 claims description 3
• 125000002883 imidazolyl group Chemical group 0.000 claims description 3
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 3
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 3
• 125000001544 thienyl group Chemical group 0.000 claims description 3
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
• IYPXINUXUQCPAS-UHFFFAOYSA-N 1-(6-aminopyrimidin-4-yl)-n-(4-bromo-2,6-dimethylphenyl)benzimidazol-2-amine Chemical compound CC1=CC(Br)=CC(C)=C1NC1=NC2=CC=CC=C2N1C1=CC(N)=NC=N1 IYPXINUXUQCPAS-UHFFFAOYSA-N 0.000 claims description 2
• VICXLLUFBVZJII-UHFFFAOYSA-N 1-(6-aminopyrimidin-4-yl)-n-(4-bromo-2-methylphenyl)benzimidazol-2-amine Chemical compound CC1=CC(Br)=CC=C1NC1=NC2=CC=CC=C2N1C1=CC(N)=NC=N1 VICXLLUFBVZJII-UHFFFAOYSA-N 0.000 claims description 2
• CZTBVXSLJFITNQ-UHFFFAOYSA-N 1-(6-aminopyrimidin-4-yl)-n-[2-(trifluoromethoxy)phenyl]benzimidazol-2-amine Chemical compound C1=NC(N)=CC(N2C3=CC=CC=C3N=C2NC=2C(=CC=CC=2)OC(F)(F)F)=N1 CZTBVXSLJFITNQ-UHFFFAOYSA-N 0.000 claims description 2
• QRWZFUBHOQWUGH-UHFFFAOYSA-N 2,5-dimethylpyrazole-3-carboxylic acid Chemical compound CC=1C=C(C(O)=O)N(C)N=1 QRWZFUBHOQWUGH-UHFFFAOYSA-N 0.000 claims description 2
• 125000003635 2-dimethylaminoethoxy group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])O* 0.000 claims description 2
• PFIQMKZHLWNUCL-UHFFFAOYSA-N 3-[[1-(6-aminopyrimidin-4-yl)benzimidazol-2-yl]amino]-n-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-4-methylbenzamide Chemical compound C1CN(CC)CCN1CC(C(=C1)C(F)(F)F)=CC=C1NC(=O)C1=CC=C(C)C(NC=2N(C3=CC=CC=C3N=2)C=2N=CN=C(N)C=2)=C1 PFIQMKZHLWNUCL-UHFFFAOYSA-N 0.000 claims description 2
• NQYGSGQCRJPLIU-UHFFFAOYSA-N 4-methyl-3-n-(1-pyrimidin-4-ylbenzimidazol-2-yl)benzene-1,3-diamine Chemical compound CC1=CC=C(N)C=C1NC1=NC2=CC=CC=C2N1C1=CC=NC=N1 NQYGSGQCRJPLIU-UHFFFAOYSA-N 0.000 claims description 2
• GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 2
• 102100033479 RAF proto-oncogene serine/threonine-protein kinase Human genes 0.000 claims description 2
• 101150071831 RPS6KA1 gene Proteins 0.000 claims description 2
• MZVQCMJNVPIDEA-UHFFFAOYSA-N [CH2]CN(CC)CC Chemical group [CH2]CN(CC)CC MZVQCMJNVPIDEA-UHFFFAOYSA-N 0.000 claims description 2
• 125000001207 fluorophenyl group Chemical group 0.000 claims description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
• 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 claims description 2
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 2
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
• 125000006203 morpholinoethyl group Chemical group [H]C([H])(*)C([H])([H])N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 2
• 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 2
• MOFGIVYSUWJCHJ-UHFFFAOYSA-N n-(2-chloro-6-methylphenyl)-1-(6-morpholin-4-ylpyrimidin-4-yl)benzimidazol-2-amine Chemical compound CC1=CC=CC(Cl)=C1NC1=NC2=CC=CC=C2N1C1=CC(N2CCOCC2)=NC=N1 MOFGIVYSUWJCHJ-UHFFFAOYSA-N 0.000 claims description 2
• WGIDARPRXYQNKF-UHFFFAOYSA-N n-(4-phenoxyphenyl)-1-pyrimidin-4-ylbenzimidazol-2-amine Chemical compound C=1C=C(OC=2C=CC=CC=2)C=CC=1NC1=NC2=CC=CC=C2N1C1=CC=NC=N1 WGIDARPRXYQNKF-UHFFFAOYSA-N 0.000 claims description 2
• XZGBSCJUAQDTBL-UHFFFAOYSA-N n-[4-methyl-3-[(1-pyrimidin-4-ylbenzimidazol-2-yl)amino]phenyl]-3-(trifluoromethyl)benzamide Chemical compound C1=C(NC=2N(C3=CC=CC=C3N=2)C=2N=CN=CC=2)C(C)=CC=C1NC(=O)C1=CC=CC(C(F)(F)F)=C1 XZGBSCJUAQDTBL-UHFFFAOYSA-N 0.000 claims description 2
• GGEALBVZDVXUND-UHFFFAOYSA-N n-[4-methyl-3-[[1-(6-morpholin-4-ylpyrimidin-4-yl)benzimidazol-2-yl]amino]phenyl]-3-(trifluoromethyl)benzamide Chemical compound C1=C(NC=2N(C3=CC=CC=C3N=2)C=2N=CN=C(C=2)N2CCOCC2)C(C)=CC=C1NC(=O)C1=CC=CC(C(F)(F)F)=C1 GGEALBVZDVXUND-UHFFFAOYSA-N 0.000 claims description 2
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 2
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 2
• 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 2
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
• 125000000335 thiazolyl group Chemical group 0.000 claims description 2
• AMXFBJCSYDYPNY-UHFFFAOYSA-N 1-(6-aminopyrimidin-4-yl)-n-(2-bromo-4,6-dimethylphenyl)benzimidazol-2-amine Chemical compound BrC1=CC(C)=CC(C)=C1NC1=NC2=CC=CC=C2N1C1=CC(N)=NC=N1 AMXFBJCSYDYPNY-UHFFFAOYSA-N 0.000 claims 2
• HTEUQPWFMDGLKN-UHFFFAOYSA-N n-[3-[[1-(6-aminopyrimidin-4-yl)benzimidazol-2-yl]amino]-4-methylphenyl]-3-(4-ethylpiperazin-1-yl)-5-(trifluoromethyl)benzamide Chemical compound C1CN(CC)CCN1C1=CC(C(=O)NC=2C=C(NC=3N(C4=CC=CC=C4N=3)C=3N=CN=C(N)C=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 HTEUQPWFMDGLKN-UHFFFAOYSA-N 0.000 claims 2
• ZPRJXZVPSKFXMT-UHFFFAOYSA-N 1-(6-aminopyrimidin-4-yl)-n-(2,4,6-trimethylphenyl)benzimidazol-2-amine Chemical compound CC1=CC(C)=CC(C)=C1NC1=NC2=CC=CC=C2N1C1=CC(N)=NC=N1 ZPRJXZVPSKFXMT-UHFFFAOYSA-N 0.000 claims 1
• PGZPWMBGGPDJNU-UHFFFAOYSA-N 1-(6-aminopyrimidin-4-yl)-n-(2,5-dimethylphenyl)benzimidazol-2-amine Chemical compound CC1=CC=C(C)C(NC=2N(C3=CC=CC=C3N=2)C=2N=CN=C(N)C=2)=C1 PGZPWMBGGPDJNU-UHFFFAOYSA-N 0.000 claims 1
• KCFYRZYFGXYNKV-UHFFFAOYSA-N 1-(6-aminopyrimidin-4-yl)-n-(2-chloro-6-methylphenyl)benzimidazol-2-amine Chemical compound CC1=CC=CC(Cl)=C1NC1=NC2=CC=CC=C2N1C1=CC(N)=NC=N1 KCFYRZYFGXYNKV-UHFFFAOYSA-N 0.000 claims 1
• KOSUSJHYYOWKIU-UHFFFAOYSA-N 1-(6-aminopyrimidin-4-yl)-n-(3-bromo-2,4,6-trimethylphenyl)benzimidazol-2-amine Chemical compound CC1=C(Br)C(C)=CC(C)=C1NC1=NC2=CC=CC=C2N1C1=CC(N)=NC=N1 KOSUSJHYYOWKIU-UHFFFAOYSA-N 0.000 claims 1
• QMEQGSHLHUBJAH-UHFFFAOYSA-N 1-(6-aminopyrimidin-4-yl)-n-(4-phenoxyphenyl)benzimidazol-2-amine Chemical compound C1=NC(N)=CC(N2C3=CC=CC=C3N=C2NC=2C=CC(OC=3C=CC=CC=3)=CC=2)=N1 QMEQGSHLHUBJAH-UHFFFAOYSA-N 0.000 claims 1
• XCCPEQBWSKUFKT-UHFFFAOYSA-N 1-(6-aminopyrimidin-4-yl)-n-(4-tert-butylphenyl)benzimidazol-2-amine Chemical compound C1=CC(C(C)(C)C)=CC=C1NC1=NC2=CC=CC=C2N1C1=CC(N)=NC=N1 XCCPEQBWSKUFKT-UHFFFAOYSA-N 0.000 claims 1
• AKGZCBJCSSQLLS-UHFFFAOYSA-N 2-[4-[6-[[6-[2-(4-bromo-2-methylanilino)benzimidazol-1-yl]pyrimidin-4-yl]amino]-2-methylpyrimidin-4-yl]piperazin-1-yl]ethanol Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(N=CN=1)=CC=1N(C1=CC=CC=C1N=1)C=1NC1=CC=C(Br)C=C1C AKGZCBJCSSQLLS-UHFFFAOYSA-N 0.000 claims 1
• GTBRMMWAOBROMF-UHFFFAOYSA-N 2-[4-[6-[[6-[2-(5-methoxy-2-methylanilino)benzimidazol-1-yl]pyrimidin-4-yl]amino]-2-methylpyrimidin-4-yl]piperazin-1-yl]ethanol Chemical compound COC1=CC=C(C)C(NC=2N(C3=CC=CC=C3N=2)C=2N=CN=C(NC=3N=C(C)N=C(C=3)N3CCN(CCO)CC3)C=2)=C1 GTBRMMWAOBROMF-UHFFFAOYSA-N 0.000 claims 1
• NHVGQRASKRTWLZ-UHFFFAOYSA-N 3-[[1-(6-aminopyrimidin-4-yl)benzimidazol-2-yl]amino]-4-methyl-n-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]benzamide Chemical compound C1=NC(C)=CN1C1=CC(NC(=O)C=2C=C(NC=3N(C4=CC=CC=C4N=3)C=3N=CN=C(N)C=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 NHVGQRASKRTWLZ-UHFFFAOYSA-N 0.000 claims 1
• LAXDODUPLVBDLC-UHFFFAOYSA-N 3-[[1-(6-aminopyrimidin-4-yl)benzimidazol-2-yl]amino]-4-methyl-n-[3-(trifluoromethyl)phenyl]benzamide Chemical compound CC1=CC=C(C(=O)NC=2C=C(C=CC=2)C(F)(F)F)C=C1NC1=NC2=CC=CC=C2N1C1=CC(N)=NC=N1 LAXDODUPLVBDLC-UHFFFAOYSA-N 0.000 claims 1
• OJANARVSPGQGCL-UHFFFAOYSA-N 3-[[1-(6-aminopyrimidin-4-yl)benzimidazol-2-yl]amino]-4-methylbenzoic acid Chemical compound CC1=CC=C(C(O)=O)C=C1NC1=NC2=CC=CC=C2N1C1=CC(N)=NC=N1 OJANARVSPGQGCL-UHFFFAOYSA-N 0.000 claims 1
• OWWGCOSIPYTEIP-UHFFFAOYSA-N 3-[[3-[6-[4-(diethylamino)butylamino]pyrimidin-4-yl]imidazo[4,5-b]pyridin-2-yl]amino]-4-methyl-n-[3-(trifluoromethyl)phenyl]benzamide Chemical compound C1=NC(NCCCCN(CC)CC)=CC(N2C3=NC=CC=C3N=C2NC=2C(=CC=C(C=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)C)=N1 OWWGCOSIPYTEIP-UHFFFAOYSA-N 0.000 claims 1
• QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims 1
• GNWMHLBUCXEXPE-UHFFFAOYSA-N 5-cyclopropyl-1h-pyrazole-3-carboxylic acid Chemical compound N1N=C(C(=O)O)C=C1C1CC1 GNWMHLBUCXEXPE-UHFFFAOYSA-N 0.000 claims 1
• 102100023794 ETS domain-containing protein Elk-3 Human genes 0.000 claims 1
• 101001048720 Homo sapiens ETS domain-containing protein Elk-3 Proteins 0.000 claims 1
• 101001092930 Homo sapiens Prosaposin Proteins 0.000 claims 1
• 101100452374 Mus musculus Ikbke gene Proteins 0.000 claims 1
• 125000005843 halogen group Chemical group 0.000 claims 1
• QBNFHYXLBWPRJZ-UHFFFAOYSA-N n-(2-chloro-6-methylphenyl)-1-[6-[2-(4-methylpiperazin-1-yl)ethylamino]pyrimidin-4-yl]benzimidazol-2-amine Chemical compound C1CN(C)CCN1CCNC1=CC(N2C3=CC=CC=C3N=C2NC=2C(=CC=CC=2C)Cl)=NC=N1 QBNFHYXLBWPRJZ-UHFFFAOYSA-N 0.000 claims 1
• KNPRFHFPAKZBIG-UHFFFAOYSA-N n-(2-chloro-6-methylphenyl)-1-[6-[[4-(morpholin-4-ylmethyl)pyridin-2-yl]amino]pyrimidin-4-yl]benzimidazol-2-amine Chemical compound CC1=CC=CC(Cl)=C1NC1=NC2=CC=CC=C2N1C1=CC(NC=2N=CC=C(CN3CCOCC3)C=2)=NC=N1 KNPRFHFPAKZBIG-UHFFFAOYSA-N 0.000 claims 1
• NFAFJKYJUBQQSU-UHFFFAOYSA-N n-(2-chloro-6-methylphenyl)-1-pyrimidin-4-ylbenzimidazol-2-amine Chemical compound CC1=CC=CC(Cl)=C1NC1=NC2=CC=CC=C2N1C1=CC=NC=N1 NFAFJKYJUBQQSU-UHFFFAOYSA-N 0.000 claims 1
• PICSDTONCAVDKS-UHFFFAOYSA-N n-(2-methylphenyl)-1-pyrimidin-4-ylbenzimidazol-2-amine Chemical compound CC1=CC=CC=C1NC1=NC2=CC=CC=C2N1C1=CC=NC=N1 PICSDTONCAVDKS-UHFFFAOYSA-N 0.000 claims 1
• GJXZJOLPUFXCCZ-UHFFFAOYSA-N n-(3,5-dichlorophenyl)-1-pyrimidin-4-ylbenzimidazol-2-amine Chemical compound ClC1=CC(Cl)=CC(NC=2N(C3=CC=CC=C3N=2)C=2N=CN=CC=2)=C1 GJXZJOLPUFXCCZ-UHFFFAOYSA-N 0.000 claims 1
• CXGURYCBXAXZNF-UHFFFAOYSA-N n-(3,5-dimethoxyphenyl)-1-[6-(4-morpholin-4-ylanilino)pyrimidin-4-yl]benzimidazol-2-amine Chemical compound COC1=CC(OC)=CC(NC=2N(C3=CC=CC=C3N=2)C=2N=CN=C(NC=3C=CC(=CC=3)N3CCOCC3)C=2)=C1 CXGURYCBXAXZNF-UHFFFAOYSA-N 0.000 claims 1
• QJHCDMJHHLYGOJ-UHFFFAOYSA-N n-[3-[[1-(6-aminopyrimidin-4-yl)benzimidazol-2-yl]amino]-4-methylphenyl]-3-[(4-ethylpiperazin-1-yl)methyl]-5-(trifluoromethyl)benzamide Chemical compound C1CN(CC)CCN1CC1=CC(C(=O)NC=2C=C(NC=3N(C4=CC=CC=C4N=3)C=3N=CN=C(N)C=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 QJHCDMJHHLYGOJ-UHFFFAOYSA-N 0.000 claims 1
• KXTIIOOGQPWWGE-UHFFFAOYSA-N n-[3-[[1-(6-aminopyrimidin-4-yl)benzimidazol-2-yl]amino]-4-methylphenyl]-3-chloro-4-[(4-ethylpiperazin-1-yl)methyl]benzamide Chemical compound C1CN(CC)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N(C4=CC=CC=C4N=3)C=3N=CN=C(N)C=3)C(C)=CC=2)C=C1Cl KXTIIOOGQPWWGE-UHFFFAOYSA-N 0.000 claims 1
• AYZBGELVIWCHIM-UHFFFAOYSA-N n-[3-[[1-(6-aminopyrimidin-4-yl)benzimidazol-2-yl]amino]-4-methylphenyl]-3-methylbenzamide Chemical compound CC1=CC=CC(C(=O)NC=2C=C(NC=3N(C4=CC=CC=C4N=3)C=3N=CN=C(N)C=3)C(C)=CC=2)=C1 AYZBGELVIWCHIM-UHFFFAOYSA-N 0.000 claims 1
• ZMLDJYQUOIGKDY-UHFFFAOYSA-N n-[3-[[1-(6-aminopyrimidin-4-yl)benzimidazol-2-yl]amino]-4-methylphenyl]-4-(2-methylimidazol-1-yl)-3-(trifluoromethyl)benzamide Chemical compound CC1=NC=CN1C1=CC=C(C(=O)NC=2C=C(NC=3N(C4=CC=CC=C4N=3)C=3N=CN=C(N)C=3)C(C)=CC=2)C=C1C(F)(F)F ZMLDJYQUOIGKDY-UHFFFAOYSA-N 0.000 claims 1
• NWSIWGBYWGMCQL-UHFFFAOYSA-N n-[3-[[1-(6-aminopyrimidin-4-yl)benzimidazol-2-yl]amino]-4-methylphenyl]-4-morpholin-4-yl-3-(trifluoromethyl)benzamide Chemical compound C1=C(NC=2N(C3=CC=CC=C3N=2)C=2N=CN=C(N)C=2)C(C)=CC=C1NC(=O)C(C=C1C(F)(F)F)=CC=C1N1CCOCC1 NWSIWGBYWGMCQL-UHFFFAOYSA-N 0.000 claims 1
• QJJCDXBVFBLEDI-UHFFFAOYSA-N n-[3-[[1-(6-chloro-5-methylpyrimidin-4-yl)benzimidazol-2-yl]amino]-4-methylphenyl]-3-(trifluoromethyl)benzamide Chemical compound C1=C(NC=2N(C3=CC=CC=C3N=2)C=2C(=C(Cl)N=CN=2)C)C(C)=CC=C1NC(=O)C1=CC=CC(C(F)(F)F)=C1 QJJCDXBVFBLEDI-UHFFFAOYSA-N 0.000 claims 1
• KNHQCAPUHAYVMO-UHFFFAOYSA-N n-[3-[[1-(6-chloropyrimidin-4-yl)benzimidazol-2-yl]amino]-4-methylphenyl]-3-(trifluoromethyl)benzamide Chemical compound C1=C(NC=2N(C3=CC=CC=C3N=2)C=2N=CN=C(Cl)C=2)C(C)=CC=C1NC(=O)C1=CC=CC(C(F)(F)F)=C1 KNHQCAPUHAYVMO-UHFFFAOYSA-N 0.000 claims 1
• WLXHZMYOVDOALX-UHFFFAOYSA-N n-[3-[[1-[6-(2-methoxyethylamino)pyrimidin-4-yl]benzimidazol-2-yl]amino]-4-methylphenyl]-3-(trifluoromethyl)benzamide Chemical compound C1=NC(NCCOC)=CC(N2C3=CC=CC=C3N=C2NC=2C(=CC=C(NC(=O)C=3C=C(C=CC=3)C(F)(F)F)C=2)C)=N1 WLXHZMYOVDOALX-UHFFFAOYSA-N 0.000 claims 1
• IPLUMIOMIKMDMG-UHFFFAOYSA-N n-[3-[[1-[6-[(1-hydroxy-3-methylbutan-2-yl)amino]pyrimidin-4-yl]benzimidazol-2-yl]amino]-4-methylphenyl]-3-(trifluoromethyl)benzamide Chemical compound C1=NC(NC(CO)C(C)C)=CC(N2C3=CC=CC=C3N=C2NC=2C(=CC=C(NC(=O)C=3C=C(C=CC=3)C(F)(F)F)C=2)C)=N1 IPLUMIOMIKMDMG-UHFFFAOYSA-N 0.000 claims 1
• REZFVUNAFUHYBW-UHFFFAOYSA-N n-[3-[[1-[6-[(4-aminocyclohexyl)amino]pyrimidin-4-yl]benzimidazol-2-yl]amino]-4-methylphenyl]-3-(trifluoromethyl)benzamide Chemical compound C1=C(NC=2N(C3=CC=CC=C3N=2)C=2N=CN=C(NC3CCC(N)CC3)C=2)C(C)=CC=C1NC(=O)C1=CC=CC(C(F)(F)F)=C1 REZFVUNAFUHYBW-UHFFFAOYSA-N 0.000 claims 1
• FITNUKNIUJHPPH-UHFFFAOYSA-N n-[3-[[1-[6-[4-(diethylamino)butylamino]pyrimidin-4-yl]benzimidazol-2-yl]amino]-4-methylphenyl]-3-(trifluoromethyl)benzamide Chemical compound C1=NC(NCCCCN(CC)CC)=CC(N2C3=CC=CC=C3N=C2NC=2C(=CC=C(NC(=O)C=3C=C(C=CC=3)C(F)(F)F)C=2)C)=N1 FITNUKNIUJHPPH-UHFFFAOYSA-N 0.000 claims 1
• YBNOBYHPBBOUFT-UHFFFAOYSA-N n-[3-[[1-[6-[4-(diethylamino)butylamino]pyrimidin-4-yl]benzimidazol-2-yl]amino]-4-methylphenyl]-4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)benzamide Chemical compound C1=NC(NCCCCN(CC)CC)=CC(N2C3=CC=CC=C3N=C2NC=2C(=CC=C(NC(=O)C=3C=C(C(CN4CCN(CC)CC4)=CC=3)C(F)(F)F)C=2)C)=N1 YBNOBYHPBBOUFT-UHFFFAOYSA-N 0.000 claims 1
• ONCSNTLXPGJUAI-UHFFFAOYSA-N n-[3-[[1-[6-[[4-(2-hydroxyethyl)piperazin-1-yl]amino]pyrimidin-4-yl]benzimidazol-2-yl]amino]-4-methylphenyl]-3-(trifluoromethyl)benzamide Chemical compound C1=C(NC=2N(C3=CC=CC=C3N=2)C=2N=CN=C(NN3CCN(CCO)CC3)C=2)C(C)=CC=C1NC(=O)C1=CC=CC(C(F)(F)F)=C1 ONCSNTLXPGJUAI-UHFFFAOYSA-N 0.000 claims 1
• XHZSFDNNTPIEDH-UHFFFAOYSA-N n-[4-methyl-3-[(1-pyrimidin-4-ylbenzimidazol-2-yl)amino]phenyl]-3-piperidin-4-yloxy-5-(trifluoromethyl)benzamide Chemical compound C1=C(NC=2N(C3=CC=CC=C3N=2)C=2N=CN=CC=2)C(C)=CC=C1NC(=O)C(C=C(C=1)C(F)(F)F)=CC=1OC1CCNCC1 XHZSFDNNTPIEDH-UHFFFAOYSA-N 0.000 claims 1
• UOJGMLQOPYVDAD-UHFFFAOYSA-N n-[4-methyl-3-[[1-[6-(3-morpholin-4-ylpropylamino)pyrimidin-4-yl]benzimidazol-2-yl]amino]phenyl]-3-(trifluoromethyl)benzamide Chemical compound C1=C(NC=2N(C3=CC=CC=C3N=2)C=2N=CN=C(NCCCN3CCOCC3)C=2)C(C)=CC=C1NC(=O)C1=CC=CC(C(F)(F)F)=C1 UOJGMLQOPYVDAD-UHFFFAOYSA-N 0.000 claims 1
• QQVLIPDYPZXRET-UHFFFAOYSA-N n-[4-methyl-3-[[1-[6-[(1-methylpiperidin-4-yl)amino]pyrimidin-4-yl]benzimidazol-2-yl]amino]phenyl]-3-(trifluoromethyl)benzamide Chemical compound C1CN(C)CCC1NC1=CC(N2C3=CC=CC=C3N=C2NC=2C(=CC=C(NC(=O)C=3C=C(C=CC=3)C(F)(F)F)C=2)C)=NC=N1 QQVLIPDYPZXRET-UHFFFAOYSA-N 0.000 claims 1
• XAWZDGHYUZKTTO-UHFFFAOYSA-N n-[4-methyl-3-[[1-[6-[(4-methylpiperazin-1-yl)amino]pyrimidin-4-yl]benzimidazol-2-yl]amino]phenyl]-3-(trifluoromethyl)benzamide Chemical compound C1CN(C)CCN1NC1=CC(N2C3=CC=CC=C3N=C2NC=2C(=CC=C(NC(=O)C=3C=C(C=CC=3)C(F)(F)F)C=2)C)=NC=N1 XAWZDGHYUZKTTO-UHFFFAOYSA-N 0.000 claims 1
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
• 125000005302 thiazolylmethyl group Chemical group [H]C1=C([H])N=C(S1)C([H])([H])* 0.000 claims 1
• 238000000034 method Methods 0.000 abstract description 20
• 230000002401 inhibitory effect Effects 0.000 abstract description 2
• 201000006417 multiple sclerosis Diseases 0.000 description 85
• 210000004027 cell Anatomy 0.000 description 67
• 230000000694 effects Effects 0.000 description 38
• 206010028980 Neoplasm Diseases 0.000 description 30
• WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 description 27
• 239000000203 mixture Substances 0.000 description 18
• 230000035772 mutation Effects 0.000 description 16
• 238000006243 chemical reaction Methods 0.000 description 15
• 230000005764 inhibitory process Effects 0.000 description 15
• 239000000243 solution Substances 0.000 description 15
• 101100268648 Mus musculus Abl1 gene Proteins 0.000 description 13
• 201000011510 cancer Diseases 0.000 description 13
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
• 239000003795 chemical substances by application Substances 0.000 description 12
• KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 12
• 239000011541 reaction mixture Substances 0.000 description 12
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 11
• 108010055717 JNK Mitogen-Activated Protein Kinases Proteins 0.000 description 11
• 102000019145 JUN kinase activity proteins Human genes 0.000 description 11
• 230000004913 activation Effects 0.000 description 11
• 230000015572 biosynthetic process Effects 0.000 description 11
• 239000000872 buffer Substances 0.000 description 11
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 10
• 102000001253 Protein Kinase Human genes 0.000 description 10
• 102000001788 Proto-Oncogene Proteins c-raf Human genes 0.000 description 10
• 230000014509 gene expression Effects 0.000 description 10
• 230000035755 proliferation Effects 0.000 description 10
• 108060006633 protein kinase Proteins 0.000 description 10
• 238000003786 synthesis reaction Methods 0.000 description 10
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 9
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
• 102000043136 MAP kinase family Human genes 0.000 description 9
• 108091054455 MAP kinase family Proteins 0.000 description 9
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
• 239000003112 inhibitor Substances 0.000 description 9
• 230000002062 proliferating effect Effects 0.000 description 9
• 108090000623 proteins and genes Proteins 0.000 description 9
• SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 description 9
• 239000000758 substrate Substances 0.000 description 9
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 8
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
• 230000002159 abnormal effect Effects 0.000 description 8
• 238000000746 purification Methods 0.000 description 8
• 238000012360 testing method Methods 0.000 description 8
• 102100023274 Dual specificity mitogen-activated protein kinase kinase 4 Human genes 0.000 description 7
• 101000935548 Homo sapiens Cytoplasmic tyrosine-protein kinase BMX Proteins 0.000 description 7
• 101001115395 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 4 Proteins 0.000 description 7
• 101000606502 Homo sapiens Protein-tyrosine kinase 6 Proteins 0.000 description 7
• 101100381649 Mus musculus Bik gene Proteins 0.000 description 7
• 101100381845 Mus musculus Blk gene Proteins 0.000 description 7
• 238000005481 NMR spectroscopy Methods 0.000 description 7
• 102100039810 Protein-tyrosine kinase 6 Human genes 0.000 description 7
• 239000002253 acid Substances 0.000 description 7
• 239000004480 active ingredient Substances 0.000 description 7
• 230000001413 cellular effect Effects 0.000 description 7
• 150000002431 hydrogen Chemical group 0.000 description 7
• 230000001105 regulatory effect Effects 0.000 description 7
• 206010039073 rheumatoid arthritis Diseases 0.000 description 7
• 201000001320 Atherosclerosis Diseases 0.000 description 6
• 208000023275 Autoimmune disease Diseases 0.000 description 6
• 102100023401 Dual specificity mitogen-activated protein kinase kinase 6 Human genes 0.000 description 6
• 101000624426 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 6 Proteins 0.000 description 6
• 101000922131 Homo sapiens Tyrosine-protein kinase CSK Proteins 0.000 description 6
• 108700012928 MAPK14 Proteins 0.000 description 6
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
• 102000054819 Mitogen-activated protein kinase 14 Human genes 0.000 description 6
• 101100323015 Mus musculus Alk gene Proteins 0.000 description 6
• 108091008606 PDGF receptors Proteins 0.000 description 6
• 201000004681 Psoriasis Diseases 0.000 description 6
• 101001045447 Synechocystis sp. (strain PCC 6803 / Kazusa) Sensor histidine kinase Hik2 Proteins 0.000 description 6
• 238000003556 assay Methods 0.000 description 6
• 230000004663 cell proliferation Effects 0.000 description 6
• 238000001914 filtration Methods 0.000 description 6
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
• 230000019491 signal transduction Effects 0.000 description 6
• 238000003756 stirring Methods 0.000 description 6
• 238000005406 washing Methods 0.000 description 6
• 101150053778 CSF1R gene Proteins 0.000 description 5
• 101100503636 Danio rerio fyna gene Proteins 0.000 description 5
• 101150018272 FYN gene Proteins 0.000 description 5
• 101001050288 Homo sapiens Transcription factor Jun Proteins 0.000 description 5
• 239000005517 L01XE01 - Imatinib Substances 0.000 description 5
• 101100381978 Mus musculus Braf gene Proteins 0.000 description 5
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
• 102220466866 Podocin_T315I_mutation Human genes 0.000 description 5
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 5
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 5
• 239000006180 TBST buffer Substances 0.000 description 5
• 239000002585 base Substances 0.000 description 5
• 101150060629 def gene Proteins 0.000 description 5
• 235000019439 ethyl acetate Nutrition 0.000 description 5
• 229940080856 gleevec Drugs 0.000 description 5
• 201000001441 melanoma Diseases 0.000 description 5
• 230000007170 pathology Effects 0.000 description 5
• 230000037361 pathway Effects 0.000 description 5
• 230000008569 process Effects 0.000 description 5
• 229940002612 prodrug Drugs 0.000 description 5
• 239000000651 prodrug Substances 0.000 description 5
• 102000004169 proteins and genes Human genes 0.000 description 5
• 230000002829 reductive effect Effects 0.000 description 5
• 239000000725 suspension Substances 0.000 description 5
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 5
• 229940124597 therapeutic agent Drugs 0.000 description 5
• KKVYYGGCHJGEFJ-UHFFFAOYSA-N 1-n-(4-chlorophenyl)-6-methyl-5-n-[3-(7h-purin-6-yl)pyridin-2-yl]isoquinoline-1,5-diamine Chemical compound N=1C=CC2=C(NC=3C(=CC=CN=3)C=3C=4N=CNC=4N=CN=3)C(C)=CC=C2C=1NC1=CC=C(Cl)C=C1 KKVYYGGCHJGEFJ-UHFFFAOYSA-N 0.000 description 4
• 108020004414 DNA Proteins 0.000 description 4
• 101001026790 Homo sapiens Tyrosine-protein kinase Fes/Fps Proteins 0.000 description 4
• 208000007766 Kaposi sarcoma Diseases 0.000 description 4
• 150000001204 N-oxides Chemical class 0.000 description 4
• 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 4
• 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 4
• 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 4
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
• 102100023132 Transcription factor Jun Human genes 0.000 description 4
• 102100037333 Tyrosine-protein kinase Fes/Fps Human genes 0.000 description 4
• 230000006907 apoptotic process Effects 0.000 description 4
• 208000006673 asthma Diseases 0.000 description 4
• 230000005754 cellular signaling Effects 0.000 description 4
• 231100000673 dose–response relationship Toxicity 0.000 description 4
• 230000012010 growth Effects 0.000 description 4
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
• 208000027866 inflammatory disease Diseases 0.000 description 4
• 230000003211 malignant effect Effects 0.000 description 4
• 238000004519 manufacturing process Methods 0.000 description 4
• 239000002609 medium Substances 0.000 description 4
• 230000001575 pathological effect Effects 0.000 description 4
• 230000026731 phosphorylation Effects 0.000 description 4
• 238000006366 phosphorylation reaction Methods 0.000 description 4
• 108090000765 processed proteins & peptides Proteins 0.000 description 4
• 125000006239 protecting group Chemical group 0.000 description 4
• 102000016914 ras Proteins Human genes 0.000 description 4
• 210000003491 skin Anatomy 0.000 description 4
• 239000002904 solvent Substances 0.000 description 4
• 230000001225 therapeutic effect Effects 0.000 description 4
• QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
• AGYCTUZXJHRHMX-UHFFFAOYSA-N 3-n-[1-(6-aminopyrimidin-4-yl)benzimidazol-2-yl]-4-methylbenzene-1,3-diamine Chemical compound CC1=CC=C(N)C=C1NC1=NC2=CC=CC=C2N1C1=CC(N)=NC=N1 AGYCTUZXJHRHMX-UHFFFAOYSA-N 0.000 description 3
• VAFIXPYRAXZBBZ-UHFFFAOYSA-N 6-(2-chlorobenzimidazol-1-yl)pyrimidin-4-amine Chemical compound C1=NC(N)=CC(N2C3=CC=CC=C3N=C2Cl)=N1 VAFIXPYRAXZBBZ-UHFFFAOYSA-N 0.000 description 3
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• 206010000830 Acute leukaemia Diseases 0.000 description 3
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 3
• 208000026310 Breast neoplasm Diseases 0.000 description 3
• 208000005623 Carcinogenesis Diseases 0.000 description 3
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 3
• 206010009944 Colon cancer Diseases 0.000 description 3
• PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 3
• 108010036949 Cyclosporine Proteins 0.000 description 3
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
• 101150036586 FES gene Proteins 0.000 description 3
• 101000932478 Homo sapiens Receptor-type tyrosine-protein kinase FLT3 Proteins 0.000 description 3
• 101000777277 Homo sapiens Serine/threonine-protein kinase Chk2 Proteins 0.000 description 3
• 101000601441 Homo sapiens Serine/threonine-protein kinase Nek2 Proteins 0.000 description 3
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
• 239000012825 JNK inhibitor Substances 0.000 description 3
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
• 101100272634 Mus musculus Bmx gene Proteins 0.000 description 3
• 101100335081 Mus musculus Flt3 gene Proteins 0.000 description 3
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
• 229920001213 Polysorbate 20 Polymers 0.000 description 3
• 102100031075 Serine/threonine-protein kinase Chk2 Human genes 0.000 description 3
• 102100037703 Serine/threonine-protein kinase Nek2 Human genes 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• 210000001744 T-lymphocyte Anatomy 0.000 description 3
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
• 102100029823 Tyrosine-protein kinase BTK Human genes 0.000 description 3
• 150000001413 amino acids Chemical class 0.000 description 3
• 230000035578 autophosphorylation Effects 0.000 description 3
• 230000033228 biological regulation Effects 0.000 description 3
• 239000012267 brine Substances 0.000 description 3
• 230000036952 cancer formation Effects 0.000 description 3
• 231100000504 carcinogenesis Toxicity 0.000 description 3
• 230000033077 cellular process Effects 0.000 description 3
• 230000036755 cellular response Effects 0.000 description 3
• 230000001684 chronic effect Effects 0.000 description 3
• 229960001265 ciclosporin Drugs 0.000 description 3
• 208000029742 colonic neoplasm Diseases 0.000 description 3
• 230000002596 correlated effect Effects 0.000 description 3
• 230000000875 corresponding effect Effects 0.000 description 3
• 230000001419 dependent effect Effects 0.000 description 3
• 230000004069 differentiation Effects 0.000 description 3
• 229940079593 drug Drugs 0.000 description 3
• 238000001952 enzyme assay Methods 0.000 description 3
• 230000005284 excitation Effects 0.000 description 3
• 239000000284 extract Substances 0.000 description 3
• 239000000706 filtrate Substances 0.000 description 3
• 238000009472 formulation Methods 0.000 description 3
• 239000012458 free base Substances 0.000 description 3
• 230000006870 function Effects 0.000 description 3
• 231100000024 genotoxic Toxicity 0.000 description 3
• 230000001738 genotoxic effect Effects 0.000 description 3
• 150000004677 hydrates Chemical class 0.000 description 3
• 238000005984 hydrogenation reaction Methods 0.000 description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
• 230000003902 lesion Effects 0.000 description 3
• 208000032839 leukemia Diseases 0.000 description 3
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
• 235000019341 magnesium sulphate Nutrition 0.000 description 3
• 239000012528 membrane Substances 0.000 description 3
• 231100000590 oncogenic Toxicity 0.000 description 3
• 230000002246 oncogenic effect Effects 0.000 description 3
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 3
• 239000013641 positive control Substances 0.000 description 3
• 239000000843 powder Substances 0.000 description 3
• 238000000926 separation method Methods 0.000 description 3
• 238000013207 serial dilution Methods 0.000 description 3
• 230000011664 signaling Effects 0.000 description 3
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
• 239000007787 solid Substances 0.000 description 3
• 238000002560 therapeutic procedure Methods 0.000 description 3
• 210000001519 tissue Anatomy 0.000 description 3
• 230000014616 translation Effects 0.000 description 3
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 2
• CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 2
• 238000005160 1H NMR spectroscopy Methods 0.000 description 2
• ATCJJYTXTIMVHF-UHFFFAOYSA-N 2-chloro-1-(6-chloropyrimidin-4-yl)benzimidazole Chemical compound ClC1=NC2=CC=CC=C2N1C1=CC(Cl)=NC=N1 ATCJJYTXTIMVHF-UHFFFAOYSA-N 0.000 description 2
• MOZVQBDPJWUYPX-UHFFFAOYSA-N 2-methyl-1-[4-nitro-2-(trifluoromethyl)phenyl]imidazole Chemical compound CC1=NC=CN1C1=CC=C([N+]([O-])=O)C=C1C(F)(F)F MOZVQBDPJWUYPX-UHFFFAOYSA-N 0.000 description 2
• CADONHSBCCZGPL-UHFFFAOYSA-N 3-amino-4-methyl-n-[4-(2-methylimidazol-1-yl)-3-(trifluoromethyl)phenyl]benzamide Chemical compound CC1=NC=CN1C(C(=C1)C(F)(F)F)=CC=C1NC(=O)C1=CC=C(C)C(N)=C1 CADONHSBCCZGPL-UHFFFAOYSA-N 0.000 description 2
• WHLQHPOULXZENK-UHFFFAOYSA-N 4-(2-methylimidazol-1-yl)-3-(trifluoromethyl)aniline Chemical compound CC1=NC=CN1C1=CC=C(N)C=C1C(F)(F)F WHLQHPOULXZENK-UHFFFAOYSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
• 206010006187 Breast cancer Diseases 0.000 description 2
• 208000024172 Cardiovascular disease Diseases 0.000 description 2
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 2
• 229930105110 Cyclosporin A Natural products 0.000 description 2
• 108090000695 Cytokines Proteins 0.000 description 2
• 102000004127 Cytokines Human genes 0.000 description 2
• 230000033616 DNA repair Effects 0.000 description 2
• 206010012689 Diabetic retinopathy Diseases 0.000 description 2
• 102100030011 Endoribonuclease Human genes 0.000 description 2
• 101710199605 Endoribonuclease Proteins 0.000 description 2
• 102000004190 Enzymes Human genes 0.000 description 2
• 108090000790 Enzymes Proteins 0.000 description 2
• 108010055196 EphA2 Receptor Proteins 0.000 description 2
• 108010055334 EphB2 Receptor Proteins 0.000 description 2
• 102100030340 Ephrin type-A receptor 2 Human genes 0.000 description 2
• 102100031968 Ephrin type-B receptor 2 Human genes 0.000 description 2
• 102100031983 Ephrin type-B receptor 4 Human genes 0.000 description 2
• 101100127166 Escherichia coli (strain K12) kefB gene Proteins 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• 101000950669 Homo sapiens Mitogen-activated protein kinase 9 Proteins 0.000 description 2
• 101001074439 Homo sapiens Polycystin-2 Proteins 0.000 description 2
• 101000945096 Homo sapiens Ribosomal protein S6 kinase alpha-5 Proteins 0.000 description 2
• 101000880439 Homo sapiens Serine/threonine-protein kinase 3 Proteins 0.000 description 2
• 101001026882 Homo sapiens Serine/threonine-protein kinase D2 Proteins 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
• 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 description 2
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
• 206010027476 Metastases Diseases 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• 102100037809 Mitogen-activated protein kinase 9 Human genes 0.000 description 2
• 241000699666 Mus <mouse, genus> Species 0.000 description 2
• 241000699670 Mus sp. Species 0.000 description 2
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 2
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
• 206010029113 Neovascularisation Diseases 0.000 description 2
• 102000007339 Nerve Growth Factor Receptors Human genes 0.000 description 2
• 108010032605 Nerve Growth Factor Receptors Proteins 0.000 description 2
• 239000000020 Nitrocellulose Substances 0.000 description 2
• 108700020796 Oncogene Proteins 0.000 description 2
• 206010061535 Ovarian neoplasm Diseases 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 2
• 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 2
• 102100020718 Receptor-type tyrosine-protein kinase FLT3 Human genes 0.000 description 2
• 102100033645 Ribosomal protein S6 kinase alpha-5 Human genes 0.000 description 2
• 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 2
• 206010039491 Sarcoma Diseases 0.000 description 2
• 101710113029 Serine/threonine-protein kinase Proteins 0.000 description 2
• 102100037628 Serine/threonine-protein kinase 3 Human genes 0.000 description 2
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
• 229920002472 Starch Polymers 0.000 description 2
• RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 2
• 230000006044 T cell activation Effects 0.000 description 2
• 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 2
• 208000007536 Thrombosis Diseases 0.000 description 2
• 108091023040 Transcription factor Proteins 0.000 description 2
• 102000040945 Transcription factor Human genes 0.000 description 2
• 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 2
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 2
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 2
• 238000004458 analytical method Methods 0.000 description 2
• 230000001028 anti-proliverative effect Effects 0.000 description 2
• 239000012300 argon atmosphere Substances 0.000 description 2
• 239000012131 assay buffer Substances 0.000 description 2
• 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 2
• 230000008901 benefit Effects 0.000 description 2
• 210000000481 breast Anatomy 0.000 description 2
• 238000004113 cell culture Methods 0.000 description 2
• 230000022131 cell cycle Effects 0.000 description 2
• 230000010261 cell growth Effects 0.000 description 2
• 210000003793 centrosome Anatomy 0.000 description 2
• 239000000460 chlorine Substances 0.000 description 2
• 101150116749 chuk gene Proteins 0.000 description 2
• 210000001072 colon Anatomy 0.000 description 2
• 239000006071 cream Substances 0.000 description 2
• 230000002074 deregulated effect Effects 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• 230000018109 developmental process Effects 0.000 description 2
• 239000003085 diluting agent Substances 0.000 description 2
• 239000006185 dispersion Substances 0.000 description 2
• 229940088598 enzyme Drugs 0.000 description 2
• 238000003818 flash chromatography Methods 0.000 description 2
• 239000000499 gel Substances 0.000 description 2
• 239000001963 growth medium Substances 0.000 description 2
• 229960002411 imatinib Drugs 0.000 description 2
• 230000002519 immonomodulatory effect Effects 0.000 description 2
• 230000028993 immune response Effects 0.000 description 2
• 230000001506 immunosuppresive effect Effects 0.000 description 2
• 238000000338 in vitro Methods 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 238000011534 incubation Methods 0.000 description 2
• 230000001939 inductive effect Effects 0.000 description 2
• 230000002757 inflammatory effect Effects 0.000 description 2
• 230000003993 interaction Effects 0.000 description 2
• 238000012417 linear regression Methods 0.000 description 2
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
• 208000019423 liver disease Diseases 0.000 description 2
• 239000012139 lysis buffer Substances 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• 108020004999 messenger RNA Proteins 0.000 description 2
• 230000009401 metastasis Effects 0.000 description 2
• 230000005012 migration Effects 0.000 description 2
• 238000013508 migration Methods 0.000 description 2
• 239000002480 mineral oil Substances 0.000 description 2
• 235000010446 mineral oil Nutrition 0.000 description 2
• 238000002156 mixing Methods 0.000 description 2
• 206010028417 myasthenia gravis Diseases 0.000 description 2
• DLDALFWGOIAFRT-UHFFFAOYSA-N n-[3-[[1-(6-aminopyrimidin-4-yl)benzimidazol-2-yl]amino]-4-methylphenyl]-3-morpholin-4-yl-5-(trifluoromethyl)benzamide Chemical compound C1=C(NC=2N(C3=CC=CC=C3N=2)C=2N=CN=C(N)C=2)C(C)=CC=C1NC(=O)C(C=C(C=1)C(F)(F)F)=CC=1N1CCOCC1 DLDALFWGOIAFRT-UHFFFAOYSA-N 0.000 description 2
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 2
• 230000001537 neural effect Effects 0.000 description 2
• 229920001220 nitrocellulos Polymers 0.000 description 2
• 102000037979 non-receptor tyrosine kinases Human genes 0.000 description 2
• 108091008046 non-receptor tyrosine kinases Proteins 0.000 description 2
• 208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
• 239000002674 ointment Substances 0.000 description 2
• 239000003960 organic solvent Substances 0.000 description 2
• 201000008482 osteoarthritis Diseases 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 2
• 102000005962 receptors Human genes 0.000 description 2
• 108020003175 receptors Proteins 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 230000002441 reversible effect Effects 0.000 description 2
• 239000000377 silicon dioxide Substances 0.000 description 2
• QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 2
• 229960002930 sirolimus Drugs 0.000 description 2
• 210000000813 small intestine Anatomy 0.000 description 2
• 210000000329 smooth muscle myocyte Anatomy 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• 239000012312 sodium hydride Substances 0.000 description 2
• 229910000104 sodium hydride Inorganic materials 0.000 description 2
• 239000012453 solvate Substances 0.000 description 2
• 239000003381 stabilizer Substances 0.000 description 2
• 235000019698 starch Nutrition 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• 210000000130 stem cell Anatomy 0.000 description 2
• UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
• 239000000126 substance Substances 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• 230000004083 survival effect Effects 0.000 description 2
• 238000013518 transcription Methods 0.000 description 2
• 230000035897 transcription Effects 0.000 description 2
• 238000010361 transduction Methods 0.000 description 2
• 230000026683 transduction Effects 0.000 description 2
• 238000013519 translation Methods 0.000 description 2
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
• 230000004614 tumor growth Effects 0.000 description 2
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 2
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
• 210000004509 vascular smooth muscle cell Anatomy 0.000 description 2
• OZFAFGSSMRRTDW-UHFFFAOYSA-N (2,4-dichlorophenyl) benzenesulfonate Chemical compound ClC1=CC(Cl)=CC=C1OS(=O)(=O)C1=CC=CC=C1 OZFAFGSSMRRTDW-UHFFFAOYSA-N 0.000 description 1
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
• FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 1
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
• LBBRKDXTUAPHJP-UHFFFAOYSA-N 1-(6-aminopyrimidin-4-yl)-n-(3,5-dichlorophenyl)benzimidazol-2-amine Chemical compound C1=NC(N)=CC(N2C3=CC=CC=C3N=C2NC=2C=C(Cl)C=C(Cl)C=2)=N1 LBBRKDXTUAPHJP-UHFFFAOYSA-N 0.000 description 1
• HBLYSHKOSXRZSF-UHFFFAOYSA-N 1-(6-aminopyrimidin-4-yl)-n-(5-bromo-2-methylphenyl)benzimidazol-2-amine Chemical compound CC1=CC=C(Br)C=C1NC1=NC2=CC=CC=C2N1C1=CC(N)=NC=N1 HBLYSHKOSXRZSF-UHFFFAOYSA-N 0.000 description 1
• DNTHMWUMRGOJRY-UHFFFAOYSA-N 1-fluoro-4-nitro-2-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC=C(F)C(C(F)(F)F)=C1 DNTHMWUMRGOJRY-UHFFFAOYSA-N 0.000 description 1
• IDINUJSAMVOPCM-UHFFFAOYSA-N 15-Deoxyspergualin Natural products NCCCNCCCCNC(=O)C(O)NC(=O)CCCCCCN=C(N)N IDINUJSAMVOPCM-UHFFFAOYSA-N 0.000 description 1
• HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical group C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
• HGUFODBRKLSHSI-UHFFFAOYSA-N 2,3,7,8-tetrachloro-dibenzo-p-dioxin Chemical compound O1C2=CC(Cl)=C(Cl)C=C2OC2=C1C=C(Cl)C(Cl)=C2 HGUFODBRKLSHSI-UHFFFAOYSA-N 0.000 description 1
• KXMUVBVMCPLCLG-UHFFFAOYSA-N 2,5-dimethoxy-n-methylbenzamide Chemical compound CNC(=O)C1=CC(OC)=CC=C1OC KXMUVBVMCPLCLG-UHFFFAOYSA-N 0.000 description 1
• AYPSHJCKSDNETA-UHFFFAOYSA-N 2-chloro-1h-benzimidazole Chemical compound C1=CC=C2NC(Cl)=NC2=C1 AYPSHJCKSDNETA-UHFFFAOYSA-N 0.000 description 1
• XTTIQGSLJBWVIV-UHFFFAOYSA-N 2-methyl-4-nitroaniline Chemical compound CC1=CC([N+]([O-])=O)=CC=C1N XTTIQGSLJBWVIV-UHFFFAOYSA-N 0.000 description 1
• WTZRQYJHRXQWTK-UHFFFAOYSA-N 2-pyrimidin-2-yl-1h-benzimidazole Chemical compound N=1C2=CC=CC=C2NC=1C1=NC=CC=N1 WTZRQYJHRXQWTK-UHFFFAOYSA-N 0.000 description 1
• XBGXGCOLWCMVOI-UHFFFAOYSA-N 3-(trifluoromethyl)benzamide Chemical compound NC(=O)C1=CC=CC(C(F)(F)F)=C1 XBGXGCOLWCMVOI-UHFFFAOYSA-N 0.000 description 1
• UPYUXTOZRFMXCW-UHFFFAOYSA-N 3-[3-(dimethylamino)pyrrolidin-1-yl]-n-[4-methyl-3-[(1-pyrimidin-4-ylbenzimidazol-2-yl)amino]phenyl]-5-(trifluoromethyl)benzamide Chemical compound C1C(N(C)C)CCN1C1=CC(C(=O)NC=2C=C(NC=3N(C4=CC=CC=C4N=3)C=3N=CN=CC=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 UPYUXTOZRFMXCW-UHFFFAOYSA-N 0.000 description 1
• 102100037263 3-phosphoinositide-dependent protein kinase 1 Human genes 0.000 description 1
• XJPZKYIHCLDXST-UHFFFAOYSA-N 4,6-dichloropyrimidine Chemical compound ClC1=CC(Cl)=NC=N1 XJPZKYIHCLDXST-UHFFFAOYSA-N 0.000 description 1
• DXMHBBURYDVYAI-UHFFFAOYSA-N 4-methyl-3-nitrobenzoyl chloride Chemical compound CC1=CC=C(C(Cl)=O)C=C1[N+]([O-])=O DXMHBBURYDVYAI-UHFFFAOYSA-N 0.000 description 1
• 102100033714 40S ribosomal protein S6 Human genes 0.000 description 1
• 102100036009 5'-AMP-activated protein kinase catalytic subunit alpha-2 Human genes 0.000 description 1
• BNMPIJWVMVNSRD-UHFFFAOYSA-N 5-methyl-1,2-oxazole-3-carboxylic acid Chemical compound CC1=CC(C(O)=O)=NO1 BNMPIJWVMVNSRD-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• 102100033793 ALK tyrosine kinase receptor Human genes 0.000 description 1
• 101150019464 ARAF gene Proteins 0.000 description 1
• 102100034134 Activin receptor type-1B Human genes 0.000 description 1
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
• 206010001258 Adenoviral infections Diseases 0.000 description 1
• 229920001817 Agar Polymers 0.000 description 1
• 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
• 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
• 108700028369 Alleles Proteins 0.000 description 1
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
• 208000024827 Alzheimer disease Diseases 0.000 description 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• 206010061424 Anal cancer Diseases 0.000 description 1
• 208000007860 Anus Neoplasms Diseases 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• 208000004736 B-Cell Leukemia Diseases 0.000 description 1
• 208000003950 B-cell lymphoma Diseases 0.000 description 1
• 230000003844 B-cell-activation Effects 0.000 description 1
• 229940124290 BCR-ABL tyrosine kinase inhibitor Drugs 0.000 description 1
• 229940124291 BTK inhibitor Drugs 0.000 description 1
• 101100222854 Bacillus subtilis (strain 168) czcO gene Proteins 0.000 description 1
• 208000023514 Barrett esophagus Diseases 0.000 description 1
• 208000023665 Barrett oesophagus Diseases 0.000 description 1
• 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
• 206010005003 Bladder cancer Diseases 0.000 description 1
• 206010005949 Bone cancer Diseases 0.000 description 1
• 208000018084 Bone neoplasm Diseases 0.000 description 1
• 201000006474 Brain Ischemia Diseases 0.000 description 1
• 206010006143 Brain stem glioma Diseases 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• JQUCWIWWWKZNCS-LESHARBVSA-N C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F Chemical compound C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F JQUCWIWWWKZNCS-LESHARBVSA-N 0.000 description 1
• 102000043139 CK2 family Human genes 0.000 description 1
• 108091054872 CK2 family Proteins 0.000 description 1
• 101100150099 Caenorhabditis elegans spk-1 gene Proteins 0.000 description 1
• 102000004657 Calcium-Calmodulin-Dependent Protein Kinase Type 2 Human genes 0.000 description 1
• 108010003721 Calcium-Calmodulin-Dependent Protein Kinase Type 2 Proteins 0.000 description 1
• 241000283707 Capra Species 0.000 description 1
• 201000009030 Carcinoma Diseases 0.000 description 1
• 208000017897 Carcinoma of esophagus Diseases 0.000 description 1
• 206010007559 Cardiac failure congestive Diseases 0.000 description 1
• 101710118321 Casein kinase I isoform alpha Proteins 0.000 description 1
• 102100034356 Casein kinase I isoform alpha-like Human genes 0.000 description 1
• ZEOWTGPWHLSLOG-UHFFFAOYSA-N Cc1ccc(cc1-c1ccc2c(n[nH]c2c1)-c1cnn(c1)C1CC1)C(=O)Nc1cccc(c1)C(F)(F)F Chemical compound Cc1ccc(cc1-c1ccc2c(n[nH]c2c1)-c1cnn(c1)C1CC1)C(=O)Nc1cccc(c1)C(F)(F)F ZEOWTGPWHLSLOG-UHFFFAOYSA-N 0.000 description 1
• 229940123587 Cell cycle inhibitor Drugs 0.000 description 1
• 206010007953 Central nervous system lymphoma Diseases 0.000 description 1
• 206010008120 Cerebral ischaemia Diseases 0.000 description 1
• 102100040428 Chitobiosyldiphosphodolichol beta-mannosyltransferase Human genes 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
• 208000015943 Coeliac disease Diseases 0.000 description 1
• 206010009900 Colitis ulcerative Diseases 0.000 description 1
• 102000000503 Collagen Type II Human genes 0.000 description 1
• 108010041390 Collagen Type II Proteins 0.000 description 1
• 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
• 208000011231 Crohn disease Diseases 0.000 description 1
• 101150069913 Csk gene Proteins 0.000 description 1
• 102000002427 Cyclin B Human genes 0.000 description 1
• 108010068150 Cyclin B Proteins 0.000 description 1
• 108010058545 Cyclin D3 Proteins 0.000 description 1
• 102000002495 Cyclin H Human genes 0.000 description 1
• 108010068237 Cyclin H Proteins 0.000 description 1
• 108010025454 Cyclin-Dependent Kinase 5 Proteins 0.000 description 1
• 108010025468 Cyclin-Dependent Kinase 6 Proteins 0.000 description 1
• 102100032857 Cyclin-dependent kinase 1 Human genes 0.000 description 1
• 101710106279 Cyclin-dependent kinase 1 Proteins 0.000 description 1
• 102100026804 Cyclin-dependent kinase 6 Human genes 0.000 description 1
• 102100026810 Cyclin-dependent kinase 7 Human genes 0.000 description 1
• 102100026805 Cyclin-dependent-like kinase 5 Human genes 0.000 description 1
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• 230000005778 DNA damage Effects 0.000 description 1
• 231100000277 DNA damage Toxicity 0.000 description 1
• 230000006820 DNA synthesis Effects 0.000 description 1
• 101100314281 Danio rerio trappc11 gene Proteins 0.000 description 1
• 108010031042 Death-Associated Protein Kinases Proteins 0.000 description 1
• 102100038605 Death-associated protein kinase 2 Human genes 0.000 description 1
• 102100038606 Death-associated protein kinase 3 Human genes 0.000 description 1
• 102100023115 Dual specificity tyrosine-phosphorylation-regulated kinase 2 Human genes 0.000 description 1
• 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 1
• 206010058314 Dysplasia Diseases 0.000 description 1
• 238000002965 ELISA Methods 0.000 description 1
• 206010014824 Endotoxic shock Diseases 0.000 description 1
• 241000402754 Erythranthe moschata Species 0.000 description 1
• 101100306202 Escherichia coli (strain K12) rpoB gene Proteins 0.000 description 1
• 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
• 241000206602 Eukaryota Species 0.000 description 1
• 208000009386 Experimental Arthritis Diseases 0.000 description 1
• 108091008794 FGF receptors Proteins 0.000 description 1
• 208000009849 Female Genital Neoplasms Diseases 0.000 description 1
• 101150040897 Fgr gene Proteins 0.000 description 1
• 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 1
• 102100023593 Fibroblast growth factor receptor 1 Human genes 0.000 description 1
• 101710182386 Fibroblast growth factor receptor 1 Proteins 0.000 description 1
• 102100023600 Fibroblast growth factor receptor 2 Human genes 0.000 description 1
• 101710182389 Fibroblast growth factor receptor 2 Proteins 0.000 description 1
• 102100027844 Fibroblast growth factor receptor 4 Human genes 0.000 description 1
• 206010016654 Fibrosis Diseases 0.000 description 1
• 101150048336 Flt1 gene Proteins 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• 102100037859 G1/S-specific cyclin-D3 Human genes 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 206010018338 Glioma Diseases 0.000 description 1
• 206010018364 Glomerulonephritis Diseases 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
• 102000009465 Growth Factor Receptors Human genes 0.000 description 1
• 108010009202 Growth Factor Receptors Proteins 0.000 description 1
• 239000007821 HATU Substances 0.000 description 1
• 101150004849 HCK gene Proteins 0.000 description 1
• 206010019280 Heart failures Diseases 0.000 description 1
• 206010056328 Hepatic ischaemia Diseases 0.000 description 1
• 208000017604 Hodgkin disease Diseases 0.000 description 1
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
• 102100032827 Homeodomain-interacting protein kinase 2 Human genes 0.000 description 1
• 101000600756 Homo sapiens 3-phosphoinositide-dependent protein kinase 1 Proteins 0.000 description 1
• 101000783681 Homo sapiens 5'-AMP-activated protein kinase catalytic subunit alpha-2 Proteins 0.000 description 1
• 101000779641 Homo sapiens ALK tyrosine kinase receptor Proteins 0.000 description 1
• 101000799189 Homo sapiens Activin receptor type-1B Proteins 0.000 description 1
• 101000891557 Homo sapiens Chitobiosyldiphosphodolichol beta-mannosyltransferase Proteins 0.000 description 1
• 101000911952 Homo sapiens Cyclin-dependent kinase 7 Proteins 0.000 description 1
• 101000956149 Homo sapiens Death-associated protein kinase 3 Proteins 0.000 description 1
• 101001049990 Homo sapiens Dual specificity tyrosine-phosphorylation-regulated kinase 2 Proteins 0.000 description 1
• 101000917134 Homo sapiens Fibroblast growth factor receptor 4 Proteins 0.000 description 1
• 101001066401 Homo sapiens Homeodomain-interacting protein kinase 2 Proteins 0.000 description 1
• 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 1
• 101000977771 Homo sapiens Interleukin-1 receptor-associated kinase 4 Proteins 0.000 description 1
• 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 1
• 101001005128 Homo sapiens LIM domain kinase 1 Proteins 0.000 description 1
• 101001063392 Homo sapiens Lymphocyte function-associated antigen 3 Proteins 0.000 description 1
• 101100457333 Homo sapiens MAPK11 gene Proteins 0.000 description 1
• 101001052493 Homo sapiens Mitogen-activated protein kinase 1 Proteins 0.000 description 1
• 101000878540 Homo sapiens Protein-tyrosine kinase 2-beta Proteins 0.000 description 1
• 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
• 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 1
• 101000944909 Homo sapiens Ribosomal protein S6 kinase alpha-1 Proteins 0.000 description 1
• 101000944921 Homo sapiens Ribosomal protein S6 kinase alpha-2 Proteins 0.000 description 1
• 101000945090 Homo sapiens Ribosomal protein S6 kinase alpha-3 Proteins 0.000 description 1
• 101000945093 Homo sapiens Ribosomal protein S6 kinase alpha-4 Proteins 0.000 description 1
• 101001051723 Homo sapiens Ribosomal protein S6 kinase alpha-6 Proteins 0.000 description 1
• 101001051714 Homo sapiens Ribosomal protein S6 kinase beta-2 Proteins 0.000 description 1
• 101000661821 Homo sapiens Serine/threonine-protein kinase 17A Proteins 0.000 description 1
• 101000777293 Homo sapiens Serine/threonine-protein kinase Chk1 Proteins 0.000 description 1
• 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
• 101000691459 Homo sapiens Serine/threonine-protein kinase N2 Proteins 0.000 description 1
• 101000588540 Homo sapiens Serine/threonine-protein kinase Nek6 Proteins 0.000 description 1
• 101000987310 Homo sapiens Serine/threonine-protein kinase PAK 2 Proteins 0.000 description 1
• 101000987297 Homo sapiens Serine/threonine-protein kinase PAK 4 Proteins 0.000 description 1
• 101000864800 Homo sapiens Serine/threonine-protein kinase Sgk1 Proteins 0.000 description 1
• 101000665442 Homo sapiens Serine/threonine-protein kinase TBK1 Proteins 0.000 description 1
• 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 1
• 101000772231 Homo sapiens Testis-specific serine/threonine-protein kinase 1 Proteins 0.000 description 1
• 101000864342 Homo sapiens Tyrosine-protein kinase BTK Proteins 0.000 description 1
• 101001050476 Homo sapiens Tyrosine-protein kinase ITK/TSK Proteins 0.000 description 1
• 101001117146 Homo sapiens [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial Proteins 0.000 description 1
• 241000714260 Human T-lymphotropic virus 1 Species 0.000 description 1
• 206010020751 Hypersensitivity Diseases 0.000 description 1
• 206010020772 Hypertension Diseases 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• 208000029462 Immunodeficiency disease Diseases 0.000 description 1
• 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 1
• 102100023533 Interleukin-1 receptor-associated kinase 4 Human genes 0.000 description 1
• 108010002350 Interleukin-2 Proteins 0.000 description 1
• 108090001005 Interleukin-6 Proteins 0.000 description 1
• 108090000862 Ion Channels Proteins 0.000 description 1
• 102000004310 Ion Channels Human genes 0.000 description 1
• 208000008839 Kidney Neoplasms Diseases 0.000 description 1
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
• 229930182816 L-glutamine Natural products 0.000 description 1
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
• 102100026023 LIM domain kinase 1 Human genes 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• 239000012448 Lithium borohydride Substances 0.000 description 1
• 108010002481 Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Proteins 0.000 description 1
• 102000036243 Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Human genes 0.000 description 1
• 102100030984 Lymphocyte function-associated antigen 3 Human genes 0.000 description 1
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
• 102100034069 MAP kinase-activated protein kinase 2 Human genes 0.000 description 1
• 101710141394 MAP kinase-activated protein kinase 2 Proteins 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 208000032271 Malignant tumor of penis Diseases 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 229910021380 Manganese Chloride Inorganic materials 0.000 description 1
• GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 206010027458 Metastases to lung Diseases 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• 101100537961 Methanosarcina mazei (strain ATCC BAA-159 / DSM 3647 / Goe1 / Go1 / JCM 11833 / OCM 88) trkA2 gene Proteins 0.000 description 1
• 108700036166 Mitogen-Activated Protein Kinase 11 Proteins 0.000 description 1
• 108700027649 Mitogen-Activated Protein Kinase 3 Proteins 0.000 description 1
• 108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 description 1
• 102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 description 1
• 102100026929 Mitogen-activated protein kinase 11 Human genes 0.000 description 1
• 108700015928 Mitogen-activated protein kinase 13 Proteins 0.000 description 1
• 102100024192 Mitogen-activated protein kinase 3 Human genes 0.000 description 1
• 102100026888 Mitogen-activated protein kinase kinase kinase 7 Human genes 0.000 description 1
• 208000034578 Multiple myelomas Diseases 0.000 description 1
• 241001529936 Murinae Species 0.000 description 1
• 101100306001 Mus musculus Mst1r gene Proteins 0.000 description 1
• 101100297651 Mus musculus Pim2 gene Proteins 0.000 description 1
• 101100091501 Mus musculus Ros1 gene Proteins 0.000 description 1
• 101710190051 Muscle, skeletal receptor tyrosine protein kinase Proteins 0.000 description 1
• 102100038168 Muscle, skeletal receptor tyrosine-protein kinase Human genes 0.000 description 1
• 201000003793 Myelodysplastic syndrome Diseases 0.000 description 1
• 102100030783 Myosin light chain kinase 3 Human genes 0.000 description 1
• 101710198035 Myosin light chain kinase, smooth muscle Proteins 0.000 description 1
• 108010052185 Myotonin-Protein Kinase Proteins 0.000 description 1
• 102100022437 Myotonin-protein kinase Human genes 0.000 description 1
• PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
• 101150111783 NTRK1 gene Proteins 0.000 description 1
• 206010029260 Neuroblastoma Diseases 0.000 description 1
• 101100436871 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) atp-3 gene Proteins 0.000 description 1
• 206010029888 Obliterative bronchiolitis Diseases 0.000 description 1
• 101100381429 Oryza sativa subsp. japonica BADH2 gene Proteins 0.000 description 1
• 208000001132 Osteoporosis Diseases 0.000 description 1
• 206010033128 Ovarian cancer Diseases 0.000 description 1
• 101150038994 PDGFRA gene Proteins 0.000 description 1
• 101150020891 PRKCA gene Proteins 0.000 description 1
• 108020002230 Pancreatic Ribonuclease Proteins 0.000 description 1
• 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
• 102000005891 Pancreatic ribonuclease Human genes 0.000 description 1
• 208000018737 Parkinson disease Diseases 0.000 description 1
• 208000031481 Pathologic Constriction Diseases 0.000 description 1
• 229930182555 Penicillin Natural products 0.000 description 1
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
• 208000002471 Penile Neoplasms Diseases 0.000 description 1
• 206010034299 Penile cancer Diseases 0.000 description 1
• 108091005804 Peptidases Proteins 0.000 description 1
• 108010058514 Phosphate-Binding Proteins Proteins 0.000 description 1
• 102000006335 Phosphate-Binding Proteins Human genes 0.000 description 1
• 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
• 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
• 208000007913 Pituitary Neoplasms Diseases 0.000 description 1
• 206010035226 Plasma cell myeloma Diseases 0.000 description 1
• 102000001393 Platelet-Derived Growth Factor alpha Receptor Human genes 0.000 description 1
• 108010068588 Platelet-Derived Growth Factor alpha Receptor Proteins 0.000 description 1
• 108010051742 Platelet-Derived Growth Factor beta Receptor Proteins 0.000 description 1
• 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• 102000004257 Potassium Channel Human genes 0.000 description 1
• 102100034368 Potassium voltage-gated channel subfamily A member 1 Human genes 0.000 description 1
• 101710154114 Potassium voltage-gated channel subfamily A member 1 Proteins 0.000 description 1
• 206010060862 Prostate cancer Diseases 0.000 description 1
• 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
• 239000004365 Protease Substances 0.000 description 1
• 102100037787 Protein-tyrosine kinase 2-beta Human genes 0.000 description 1
• 102000018471 Proto-Oncogene Proteins B-raf Human genes 0.000 description 1
• 108010091528 Proto-Oncogene Proteins B-raf Proteins 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• 101710141955 RAF proto-oncogene serine/threonine-protein kinase Proteins 0.000 description 1
• 239000012980 RPMI-1640 medium Substances 0.000 description 1
• 108091005682 Receptor kinases Proteins 0.000 description 1
• 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
• 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 1
• 208000015634 Rectal Neoplasms Diseases 0.000 description 1
• 206010038389 Renal cancer Diseases 0.000 description 1
• PLXBWHJQWKZRKG-UHFFFAOYSA-N Resazurin Chemical compound C1=CC(=O)C=C2OC3=CC(O)=CC=C3[N+]([O-])=C21 PLXBWHJQWKZRKG-UHFFFAOYSA-N 0.000 description 1
• 101150077555 Ret gene Proteins 0.000 description 1
• 208000007135 Retinal Neovascularization Diseases 0.000 description 1
• 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
• 101100091511 Rhizobium radiobacter ros gene Proteins 0.000 description 1
• 101710088411 Rho-associated protein kinase 1 Proteins 0.000 description 1
• 102100039313 Rho-associated protein kinase 1 Human genes 0.000 description 1
• 108010034782 Ribosomal Protein S6 Kinases Proteins 0.000 description 1
• 102000009738 Ribosomal Protein S6 Kinases Human genes 0.000 description 1
• 102000002278 Ribosomal Proteins Human genes 0.000 description 1
• 108010000605 Ribosomal Proteins Proteins 0.000 description 1
• 108090000221 Ribosomal protein S6 Proteins 0.000 description 1
• 102100033536 Ribosomal protein S6 kinase alpha-1 Human genes 0.000 description 1
• 102100033534 Ribosomal protein S6 kinase alpha-2 Human genes 0.000 description 1
• 102100033643 Ribosomal protein S6 kinase alpha-3 Human genes 0.000 description 1
• 102100033644 Ribosomal protein S6 kinase alpha-4 Human genes 0.000 description 1
• 102100024897 Ribosomal protein S6 kinase alpha-6 Human genes 0.000 description 1
• 102100024917 Ribosomal protein S6 kinase beta-2 Human genes 0.000 description 1
• 101150046814 SAPK2 gene Proteins 0.000 description 1
• 206010039710 Scleroderma Diseases 0.000 description 1
• 206010040070 Septic Shock Diseases 0.000 description 1
• 102100037955 Serine/threonine-protein kinase 17A Human genes 0.000 description 1
• 102100031081 Serine/threonine-protein kinase Chk1 Human genes 0.000 description 1
• 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
• 102100026180 Serine/threonine-protein kinase N2 Human genes 0.000 description 1
• 102100031401 Serine/threonine-protein kinase Nek6 Human genes 0.000 description 1
• 102100027939 Serine/threonine-protein kinase PAK 2 Human genes 0.000 description 1
• 102100027940 Serine/threonine-protein kinase PAK 4 Human genes 0.000 description 1
• 102100026715 Serine/threonine-protein kinase STK11 Human genes 0.000 description 1
• 101710181599 Serine/threonine-protein kinase STK11 Proteins 0.000 description 1
• 102100038192 Serine/threonine-protein kinase TBK1 Human genes 0.000 description 1
• 208000021386 Sjogren Syndrome Diseases 0.000 description 1
• 208000000453 Skin Neoplasms Diseases 0.000 description 1
• 206010041067 Small cell lung cancer Diseases 0.000 description 1
• 102000018674 Sodium Channels Human genes 0.000 description 1
• 108010052164 Sodium Channels Proteins 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 208000005718 Stomach Neoplasms Diseases 0.000 description 1
• 208000006011 Stroke Diseases 0.000 description 1
• 208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• 230000006052 T cell proliferation Effects 0.000 description 1
• 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 1
• 102100029350 Testis-specific serine/threonine-protein kinase 1 Human genes 0.000 description 1
• 108090000190 Thrombin Proteins 0.000 description 1
• 208000024799 Thyroid disease Diseases 0.000 description 1
• 208000024770 Thyroid neoplasm Diseases 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• 206010052779 Transplant rejections Diseases 0.000 description 1
• 208000030886 Traumatic Brain injury Diseases 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• 229920004890 Triton X-100 Polymers 0.000 description 1
• 208000026911 Tuberous sclerosis complex Diseases 0.000 description 1
• 102000001742 Tumor Suppressor Proteins Human genes 0.000 description 1
• 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
• 102100022596 Tyrosine-protein kinase ABL1 Human genes 0.000 description 1
• 102100023345 Tyrosine-protein kinase ITK/TSK Human genes 0.000 description 1
• 102100021125 Tyrosine-protein kinase ZAP-70 Human genes 0.000 description 1
• 201000006704 Ulcerative Colitis Diseases 0.000 description 1
• 206010046431 Urethral cancer Diseases 0.000 description 1
• 206010046458 Urethral neoplasms Diseases 0.000 description 1
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
• 208000002495 Uterine Neoplasms Diseases 0.000 description 1
• 201000003761 Vaginal carcinoma Diseases 0.000 description 1
• 206010047115 Vasculitis Diseases 0.000 description 1
• 208000008383 Wilms tumor Diseases 0.000 description 1
• 208000027418 Wounds and injury Diseases 0.000 description 1
• 108010046882 ZAP-70 Protein-Tyrosine Kinase Proteins 0.000 description 1
• BTKMJKKKZATLBU-UHFFFAOYSA-N [2-(1,3-benzothiazol-2-yl)-1,3-benzothiazol-6-yl] dihydrogen phosphate Chemical compound C1=CC=C2SC(C3=NC4=CC=C(C=C4S3)OP(O)(=O)O)=NC2=C1 BTKMJKKKZATLBU-UHFFFAOYSA-N 0.000 description 1
• 230000001594 aberrant effect Effects 0.000 description 1
• 239000002250 absorbent Substances 0.000 description 1
• 230000002745 absorbent Effects 0.000 description 1
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 239000012190 activator Substances 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 210000004100 adrenal gland Anatomy 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 235000010419 agar Nutrition 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• 230000007815 allergy Effects 0.000 description 1
• 230000000735 allogeneic effect Effects 0.000 description 1
• 238000011316 allogeneic transplantation Methods 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• 235000010210 aluminium Nutrition 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 150000001412 amines Chemical class 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 239000000908 ammonium hydroxide Substances 0.000 description 1
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
• 230000033115 angiogenesis Effects 0.000 description 1
• 238000002399 angioplasty Methods 0.000 description 1
• 230000000844 anti-bacterial effect Effects 0.000 description 1
• 239000002260 anti-inflammatory agent Substances 0.000 description 1
• 239000002246 antineoplastic agent Substances 0.000 description 1
• 201000011165 anus cancer Diseases 0.000 description 1
• 230000001640 apoptogenic effect Effects 0.000 description 1
• 238000003782 apoptosis assay Methods 0.000 description 1
• 230000009925 apoptotic mechanism Effects 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 239000003125 aqueous solvent Substances 0.000 description 1
• 125000000732 arylene group Chemical group 0.000 description 1
• ZDQSOHOQTUFQEM-PKUCKEGBSA-N ascomycin Chemical compound C/C([C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H]([C@H](C[C@H]2C)OC)[C@@H](OC)C[C@@H](C)C\C(C)=C/[C@H](C(C[C@H](O)[C@H]1C)=O)CC)=C\[C@@H]1CC[C@@H](O)[C@H](OC)C1 ZDQSOHOQTUFQEM-PKUCKEGBSA-N 0.000 description 1
• ZDQSOHOQTUFQEM-XCXYXIJFSA-N ascomycin Natural products CC[C@H]1C=C(C)C[C@@H](C)C[C@@H](OC)[C@H]2O[C@@](O)([C@@H](C)C[C@H]2OC)C(=O)C(=O)N3CCCC[C@@H]3C(=O)O[C@H]([C@H](C)[C@@H](O)CC1=O)C(=C[C@@H]4CC[C@@H](O)[C@H](C4)OC)C ZDQSOHOQTUFQEM-XCXYXIJFSA-N 0.000 description 1
• 230000001363 autoimmune Effects 0.000 description 1
• 201000004982 autoimmune uveitis Diseases 0.000 description 1
• 229960002170 azathioprine Drugs 0.000 description 1
• LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
• 210000003719 b-lymphocyte Anatomy 0.000 description 1
• 239000003899 bactericide agent Substances 0.000 description 1
• 230000004888 barrier function Effects 0.000 description 1
• 102000004441 bcr-abl Fusion Proteins Human genes 0.000 description 1
• 108010056708 bcr-abl Fusion Proteins Proteins 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
• 125000004600 benzothiopyranyl group Chemical group S1C(C=CC2=C1C=CC=C2)* 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000005540 biological transmission Effects 0.000 description 1
• 229960002685 biotin Drugs 0.000 description 1
• 239000011616 biotin Substances 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 210000004204 blood vessel Anatomy 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 238000009835 boiling Methods 0.000 description 1
• 230000014461 bone development Effects 0.000 description 1
• 230000008468 bone growth Effects 0.000 description 1
• 210000001185 bone marrow Anatomy 0.000 description 1
• 210000002798 bone marrow cell Anatomy 0.000 description 1
• 210000000133 brain stem Anatomy 0.000 description 1
• PHEZJEYUWHETKO-UHFFFAOYSA-N brequinar Chemical compound N1=C2C=CC(F)=CC2=C(C(O)=O)C(C)=C1C(C=C1)=CC=C1C1=CC=CC=C1F PHEZJEYUWHETKO-UHFFFAOYSA-N 0.000 description 1
• 229950010231 brequinar Drugs 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• 201000003848 bronchiolitis obliterans Diseases 0.000 description 1
• 208000023367 bronchiolitis obliterans with obstructive pulmonary disease Diseases 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 230000000747 cardiac effect Effects 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 230000030833 cell death Effects 0.000 description 1
• 230000024245 cell differentiation Effects 0.000 description 1
• 230000003915 cell function Effects 0.000 description 1
• 239000013592 cell lysate Substances 0.000 description 1
• 239000006285 cell suspension Substances 0.000 description 1
• 230000010307 cell transformation Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 210000003169 central nervous system Anatomy 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• 206010008118 cerebral infarction Diseases 0.000 description 1
• 208000019065 cervical carcinoma Diseases 0.000 description 1
• 210000003679 cervix uteri Anatomy 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• 210000001612 chondrocyte Anatomy 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• 208000037976 chronic inflammation Diseases 0.000 description 1
• 230000006020 chronic inflammation Effects 0.000 description 1
• 208000024207 chronic leukemia Diseases 0.000 description 1
• 208000019425 cirrhosis of liver Diseases 0.000 description 1
• 238000011260 co-administration Methods 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 238000004040 coloring Methods 0.000 description 1
• 239000002299 complementary DNA Substances 0.000 description 1
• 230000001143 conditioned effect Effects 0.000 description 1
• 230000006552 constitutive activation Effects 0.000 description 1
• 230000001276 controlling effect Effects 0.000 description 1
• 239000003246 corticosteroid Substances 0.000 description 1
• 229960001334 corticosteroids Drugs 0.000 description 1
• 208000030381 cutaneous melanoma Diseases 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 229960004397 cyclophosphamide Drugs 0.000 description 1
• 229930182912 cyclosporin Natural products 0.000 description 1
• 229940127089 cytotoxic agent Drugs 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• 238000000354 decomposition reaction Methods 0.000 description 1
• 230000002950 deficient Effects 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 206010012601 diabetes mellitus Diseases 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• FSBVERYRVPGNGG-UHFFFAOYSA-N dimagnesium dioxido-bis[[oxido(oxo)silyl]oxy]silane hydrate Chemical compound O.[Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O FSBVERYRVPGNGG-UHFFFAOYSA-N 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 239000003937 drug carrier Substances 0.000 description 1
• 230000002900 effect on cell Effects 0.000 description 1
• 239000012636 effector Substances 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 210000000750 endocrine system Anatomy 0.000 description 1
• 201000003914 endometrial carcinoma Diseases 0.000 description 1
• 239000003239 environmental mutagen Substances 0.000 description 1
• 238000007824 enzymatic assay Methods 0.000 description 1
• 210000002615 epidermis Anatomy 0.000 description 1
• DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
• 239000002360 explosive Substances 0.000 description 1
• 201000001343 fallopian tube carcinoma Diseases 0.000 description 1
• 239000012091 fetal bovine serum Substances 0.000 description 1
• 239000012894 fetal calf serum Substances 0.000 description 1
• 210000002950 fibroblast Anatomy 0.000 description 1
• 230000004761 fibrosis Effects 0.000 description 1
• 239000012467 final product Substances 0.000 description 1
• 238000000684 flow cytometry Methods 0.000 description 1
• 239000012530 fluid Substances 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 230000004927 fusion Effects 0.000 description 1
• 206010017758 gastric cancer Diseases 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 239000007903 gelatin capsule Substances 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 239000003862 glucocorticoid Substances 0.000 description 1
• PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
• 239000010931 gold Substances 0.000 description 1
• 229910052737 gold Inorganic materials 0.000 description 1
• 210000003714 granulocyte Anatomy 0.000 description 1
• 208000037824 growth disorder Diseases 0.000 description 1
• 239000003102 growth factor Substances 0.000 description 1
• 201000010536 head and neck cancer Diseases 0.000 description 1
• 208000014829 head and neck neoplasm Diseases 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 208000019622 heart disease Diseases 0.000 description 1
• 201000011066 hemangioma Diseases 0.000 description 1
• 201000005787 hematologic cancer Diseases 0.000 description 1
• 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
• 231100000042 hematotoxic Toxicity 0.000 description 1
• 210000001357 hemopoietic progenitor cell Anatomy 0.000 description 1
• 125000005842 heteroatom Chemical group 0.000 description 1
• 238000002868 homogeneous time resolved fluorescence Methods 0.000 description 1
• 206010020718 hyperplasia Diseases 0.000 description 1
• 230000003463 hyperproliferative effect Effects 0.000 description 1
• 230000001969 hypertrophic effect Effects 0.000 description 1
• 210000000987 immune system Anatomy 0.000 description 1
• 208000026278 immune system disease Diseases 0.000 description 1
• 238000000099 in vitro assay Methods 0.000 description 1
• 230000002779 inactivation Effects 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 239000007972 injectable composition Substances 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 208000014674 injury Diseases 0.000 description 1
• 150000007529 inorganic bases Chemical class 0.000 description 1
• 102000006495 integrins Human genes 0.000 description 1
• 108010044426 integrins Proteins 0.000 description 1
• 239000000543 intermediate Substances 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 238000011835 investigation Methods 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 208000028867 ischemia Diseases 0.000 description 1
• 239000000644 isotonic solution Substances 0.000 description 1
• 108700025907 jun Genes Proteins 0.000 description 1
• 201000010982 kidney cancer Diseases 0.000 description 1
• 208000017169 kidney disease Diseases 0.000 description 1
• 238000003674 kinase activity assay Methods 0.000 description 1
• 229940043355 kinase inhibitor Drugs 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 229960000681 leflunomide Drugs 0.000 description 1
• VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 description 1
• 210000000265 leukocyte Anatomy 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 238000004020 luminiscence type Methods 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• 201000005202 lung cancer Diseases 0.000 description 1
• 201000005296 lung carcinoma Diseases 0.000 description 1
• 208000020816 lung neoplasm Diseases 0.000 description 1
• 210000001165 lymph node Anatomy 0.000 description 1
• 210000002540 macrophage Anatomy 0.000 description 1
• 208000002780 macular degeneration Diseases 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 229910001629 magnesium chloride Inorganic materials 0.000 description 1
• 239000000391 magnesium silicate Substances 0.000 description 1
• 229910052919 magnesium silicate Inorganic materials 0.000 description 1
• 235000019792 magnesium silicate Nutrition 0.000 description 1
• 201000010893 malignant breast melanoma Diseases 0.000 description 1
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
• 239000011565 manganese chloride Substances 0.000 description 1
• 235000002867 manganese chloride Nutrition 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 239000000463 material Substances 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• 230000001394 metastastic effect Effects 0.000 description 1
• 206010061289 metastatic neoplasm Diseases 0.000 description 1
• 229960000485 methotrexate Drugs 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 125000006393 methylpyrimidinyl group Chemical group 0.000 description 1
• HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 230000011278 mitosis Effects 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 210000001616 monocyte Anatomy 0.000 description 1
• 229960004866 mycophenolate mofetil Drugs 0.000 description 1
• RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 description 1
• 229960000951 mycophenolic acid Drugs 0.000 description 1
• HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 1
• 201000005962 mycosis fungoides Diseases 0.000 description 1
• 210000000066 myeloid cell Anatomy 0.000 description 1
• 208000010125 myocardial infarction Diseases 0.000 description 1
• OLWKKJFPTCSTBF-UHFFFAOYSA-N n-(4-tert-butylphenyl)-1-pyrimidin-4-ylbenzimidazol-2-amine Chemical compound C1=CC(C(C)(C)C)=CC=C1NC1=NC2=CC=CC=C2N1C1=CC=NC=N1 OLWKKJFPTCSTBF-UHFFFAOYSA-N 0.000 description 1
• BLUYEPLOXLPVCJ-INIZCTEOSA-N n-[(1s)-2-[4-(3-aminopropylamino)butylamino]-1-hydroxyethyl]-7-(diaminomethylideneamino)heptanamide Chemical compound NCCCNCCCCNC[C@H](O)NC(=O)CCCCCCNC(N)=N BLUYEPLOXLPVCJ-INIZCTEOSA-N 0.000 description 1
• YXQXVCBCHOYWDX-UHFFFAOYSA-N n-[3-[[1-(6-aminopyrimidin-4-yl)benzimidazol-2-yl]amino]-4-methylphenyl]-3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzamide Chemical compound C1=NC(C)=CN1C1=CC(C(=O)NC=2C=C(NC=3N(C4=CC=CC=C4N=3)C=3N=CN=C(N)C=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 YXQXVCBCHOYWDX-UHFFFAOYSA-N 0.000 description 1
• SDPBPKTXHBUBMX-UHFFFAOYSA-N n-[3-[[1-[6-[4-(diethylamino)butylamino]-5-methylpyrimidin-4-yl]benzimidazol-2-yl]amino]-4-methylphenyl]-3-(trifluoromethyl)benzamide Chemical compound CCN(CC)CCCCNC1=NC=NC(N2C3=CC=CC=C3N=C2NC=2C(=CC=C(NC(=O)C=3C=C(C=CC=3)C(F)(F)F)C=2)C)=C1C SDPBPKTXHBUBMX-UHFFFAOYSA-N 0.000 description 1
• ZJEDGXGHFKCGDV-UHFFFAOYSA-N n-[3-[[1-[6-[4-(diethylamino)butylamino]pyrimidin-4-yl]benzimidazol-2-yl]amino]-4-methylphenyl]-3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzamide Chemical compound C1=NC(NCCCCN(CC)CC)=CC(N2C3=CC=CC=C3N=C2NC=2C(=CC=C(NC(=O)C=3C=C(C=C(C=3)N3C=C(C)N=C3)C(F)(F)F)C=2)C)=N1 ZJEDGXGHFKCGDV-UHFFFAOYSA-N 0.000 description 1
• NNLIMNLYBCBYQJ-UHFFFAOYSA-N n-[4-methyl-3-[(1-pyrimidin-4-ylbenzimidazol-2-yl)amino]phenyl]-3-piperazin-1-yl-5-(trifluoromethyl)benzamide Chemical compound C1=C(NC=2N(C3=CC=CC=C3N=2)C=2N=CN=CC=2)C(C)=CC=C1NC(=O)C(C=C(C=1)C(F)(F)F)=CC=1N1CCNCC1 NNLIMNLYBCBYQJ-UHFFFAOYSA-N 0.000 description 1
• JQAVGDHDTJHEOD-UHFFFAOYSA-N n-[4-methyl-3-[(1-pyrimidin-4-ylbenzimidazol-2-yl)amino]phenyl]-3-pyrrolidin-2-yloxy-5-(trifluoromethyl)benzamide Chemical compound C1=C(NC=2N(C3=CC=CC=C3N=2)C=2N=CN=CC=2)C(C)=CC=C1NC(=O)C(C=C(C=1)C(F)(F)F)=CC=1OC1CCCN1 JQAVGDHDTJHEOD-UHFFFAOYSA-N 0.000 description 1
• FILQIUCXPQZUON-UHFFFAOYSA-N n-[4-methyl-3-[[1-[6-[3-(4-methylpiperazin-1-yl)propylamino]pyrimidin-4-yl]benzimidazol-2-yl]amino]phenyl]-3-(trifluoromethyl)benzamide Chemical compound C1CN(C)CCN1CCCNC1=CC(N2C3=CC=CC=C3N=C2NC=2C(=CC=C(NC(=O)C=3C=C(C=CC=3)C(F)(F)F)C=2)C)=NC=N1 FILQIUCXPQZUON-UHFFFAOYSA-N 0.000 description 1
• JTSLALYXYSRPGW-UHFFFAOYSA-N n-[5-(4-cyanophenyl)-1h-pyrrolo[2,3-b]pyridin-3-yl]pyridine-3-carboxamide Chemical compound C=1C=CN=CC=1C(=O)NC(C1=C2)=CNC1=NC=C2C1=CC=C(C#N)C=C1 JTSLALYXYSRPGW-UHFFFAOYSA-N 0.000 description 1
• XJMUUEMSIJHHBF-UHFFFAOYSA-N n-[6-[2-(2-chloro-6-methylanilino)benzimidazol-1-yl]pyrimidin-4-yl]morpholin-4-amine Chemical compound CC1=CC=CC(Cl)=C1NC1=NC2=CC=CC=C2N1C1=CC(NN2CCOCC2)=NC=N1 XJMUUEMSIJHHBF-UHFFFAOYSA-N 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 230000001613 neoplastic effect Effects 0.000 description 1
• 201000008026 nephroblastoma Diseases 0.000 description 1
• 210000000653 nervous system Anatomy 0.000 description 1
• 230000004770 neurodegeneration Effects 0.000 description 1
• 208000015122 neurodegenerative disease Diseases 0.000 description 1
• 230000000955 neuroendocrine Effects 0.000 description 1
• ZHCAAFJSYLFLPX-UHFFFAOYSA-N nitrocyclohexatriene Chemical group [O-][N+](=O)C1=CC=C=C[CH]1 ZHCAAFJSYLFLPX-UHFFFAOYSA-N 0.000 description 1
• 231100000956 nontoxicity Toxicity 0.000 description 1
• 108020004707 nucleic acids Proteins 0.000 description 1
• 102000039446 nucleic acids Human genes 0.000 description 1
• 150000007523 nucleic acids Chemical class 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 238000011275 oncology therapy Methods 0.000 description 1
• 102000027450 oncoproteins Human genes 0.000 description 1
• 108091008819 oncoproteins Proteins 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 239000003791 organic solvent mixture Substances 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 210000002997 osteoclast Anatomy 0.000 description 1
• 210000001672 ovary Anatomy 0.000 description 1
• 230000002018 overexpression Effects 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 210000002571 pancreatic alpha cell Anatomy 0.000 description 1
• 201000002528 pancreatic cancer Diseases 0.000 description 1
• 208000008443 pancreatic carcinoma Diseases 0.000 description 1
• 230000000849 parathyroid Effects 0.000 description 1
• 210000002990 parathyroid gland Anatomy 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 239000006072 paste Substances 0.000 description 1
• 230000008506 pathogenesis Effects 0.000 description 1
• 230000001717 pathogenic effect Effects 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
• 229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 229940080469 phosphocellulose Drugs 0.000 description 1
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
• 230000000704 physical effect Effects 0.000 description 1
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 238000010837 poor prognosis Methods 0.000 description 1
• 108020001213 potassium channel Proteins 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 230000003449 preventive effect Effects 0.000 description 1
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
• 208000016800 primary central nervous system lymphoma Diseases 0.000 description 1
• 239000000047 product Substances 0.000 description 1
• 230000005522 programmed cell death Effects 0.000 description 1
• XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 1
• 210000002307 prostate Anatomy 0.000 description 1
• 210000005267 prostate cell Anatomy 0.000 description 1
• 208000023958 prostate neoplasm Diseases 0.000 description 1
• 229960000856 protein c Drugs 0.000 description 1
• 208000005069 pulmonary fibrosis Diseases 0.000 description 1
• 125000006513 pyridinyl methyl group Chemical group 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 108700042226 ras Genes Proteins 0.000 description 1
• 239000003642 reactive oxygen metabolite Substances 0.000 description 1
• 230000009257 reactivity Effects 0.000 description 1
• 238000011084 recovery Methods 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 206010038038 rectal cancer Diseases 0.000 description 1
• 201000001275 rectum cancer Diseases 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 230000022983 regulation of cell cycle Effects 0.000 description 1
• 230000024122 regulation of cell motility Effects 0.000 description 1
• 208000037803 restenosis Diseases 0.000 description 1
• 208000032253 retinal ischemia Diseases 0.000 description 1
• 125000006413 ring segment Chemical group 0.000 description 1
• 102220196678 rs1057518858 Human genes 0.000 description 1
• 102200135505 rs2273535 Human genes 0.000 description 1
• 102220094066 rs876659747 Human genes 0.000 description 1
• 201000000306 sarcoidosis Diseases 0.000 description 1
• 230000035945 sensitivity Effects 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 239000012679 serum free medium Substances 0.000 description 1
• 239000000741 silica gel Substances 0.000 description 1
• 229910002027 silica gel Inorganic materials 0.000 description 1
• 201000000849 skin cancer Diseases 0.000 description 1
• 208000017520 skin disease Diseases 0.000 description 1
• 201000003708 skin melanoma Diseases 0.000 description 1
• 208000000587 small cell lung carcinoma Diseases 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 235000015424 sodium Nutrition 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 230000020347 spindle assembly Effects 0.000 description 1
• 210000000952 spleen Anatomy 0.000 description 1
• 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 230000036262 stenosis Effects 0.000 description 1
• 208000037804 stenosis Diseases 0.000 description 1
• 201000011549 stomach cancer Diseases 0.000 description 1
• 229960005322 streptomycin Drugs 0.000 description 1
• 125000005415 substituted alkoxy group Chemical group 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
• 229910052717 sulfur Inorganic materials 0.000 description 1
• 239000011593 sulfur Substances 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 208000024891 symptom Diseases 0.000 description 1
• 208000011580 syndromic disease Diseases 0.000 description 1
• 230000002195 synergetic effect Effects 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 108091008743 testicular receptors 4 Proteins 0.000 description 1
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 230000008719 thickening Effects 0.000 description 1
• 229960004072 thrombin Drugs 0.000 description 1
• 201000002510 thyroid cancer Diseases 0.000 description 1
• 208000021510 thyroid gland disease Diseases 0.000 description 1
• 230000017423 tissue regeneration Effects 0.000 description 1
• 239000012443 tonicity enhancing agent Substances 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 238000000844 transformation Methods 0.000 description 1
• 230000007704 transition Effects 0.000 description 1
• 238000002054 transplantation Methods 0.000 description 1
• 230000009529 traumatic brain injury Effects 0.000 description 1
• 238000011269 treatment regimen Methods 0.000 description 1
• 125000004306 triazinyl group Chemical group 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• 101150025395 trkA gene Proteins 0.000 description 1
• 101150113435 trkA1 gene Proteins 0.000 description 1
• 102000047459 trkC Receptor Human genes 0.000 description 1
• 108010064892 trkC Receptor Proteins 0.000 description 1
• 208000009999 tuberous sclerosis Diseases 0.000 description 1
• 230000001173 tumoral effect Effects 0.000 description 1
• 230000001875 tumorinhibitory effect Effects 0.000 description 1
• 210000004026 tunica intima Anatomy 0.000 description 1
• 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
• 210000000626 ureter Anatomy 0.000 description 1
• 201000007433 ureter carcinoma Diseases 0.000 description 1
• 201000005112 urinary bladder cancer Diseases 0.000 description 1
• 206010046766 uterine cancer Diseases 0.000 description 1
• 208000037965 uterine sarcoma Diseases 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 208000013013 vulvar carcinoma Diseases 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1